Phillip Stricker

Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort

Publisher: Elsevier BV

Date: 06-2020

DOI: 10.1016/J.EUO.2019.04.008

Abstract: Focal irreversible electroporation (IRE) can be used to treat men with localised prostate cancer (PCa) with reduced impact on quality of life (QoL). To assess oncological and functional outcomes. To report on a prospective database of patients undergoing primary IRE between February 2013 and August 2018. A minimum of 12-mo follow-up was available for 123 patients. Median follow-up was 36 mo (interquartile range [IQR] 24-52 mo). A total of 112 (91%) patients had National Comprehensive Cancer Network intermediate risk and 11 (9%) had low risk. A total of 12 (9.8%) had International Society of Urological Pathology (ISUP) grade 1, 88 (71.5%) had ISUP 2, and 23 (18.7%) had ISUP 3. Focal IRE ablation of PCa lesions. Follow-up involved serial prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and transperineal template mapping biopsy (TTMB) at 12 mo. Failure-free survival (FFS) was defined as progression to whole-gland or systemic treatment or metastasis/death. Functional outcomes were assessed. Median age was 68yr (IQR 62-73yr). Median preoperative PSA was 5.7ng/ml (IQR 3.8-8.0ng/ml). On post-treatment TTMB, in-field recurrence was present in 2.7-9.8% of patients. FFS at 3yr was 96.75%, metastasis-free survival 99%, and overall survival 100%. A total of 18 patients required salvage treatment (12 had repeat IRE six had whole-gland treatment). The negative predictive value of mpMRI was 94% and sensitivity 40% for detecting in-field residual disease 6 mo after treatment. Among patients who returned questionnaires, 80/81 (98.8%) remained pad free and 40/53 (76%) had no change in erectile function. Focal IRE in select patients with localised clinically significant PCa has satisfactory short-term oncological outcomes with a minimal impact on patient QoL. In this study, 123 patients underwent focal therapy using irreversible electroporation. Follow-up biopsy was clear of residual disease in 90.2-97.3% of patients. Of patients, 96.75% avoided whole gland treatment at 3yr.

Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer.

Publisher: Wiley

Date: 18-06-2016

DOI: 10.1111/BJU.13540

Abstract: To assess the accuracy of 68Gallium-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in intermediate- and high-risk prostate cancer (PCa). From April to October 2015, 30 patients with intermediate- (n = 3) or high-risk (n = 27) PCa were prospectively enrolled. Patients underwent preoperative 68Ga-PSMA PET/CT. Both visual and semi-quantitative analyses were undertaken. Subsequently, all patients underwent radical prostatectomy (RP) with an extended pelvic lymph node dissection. The sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for LN status of 68Ga-PSMA were calculated using histopathology as reference. Eleven patients (37%) had lymph node metastases (LNMs) 26 LNMs were identified in the 11 patients. Patient analysis showed that 68Ga-PSMA PET/CT had a sensitivity of 64% for the detection of LNMs, its specificity was 95%, the PPV was 88%, and the NPV was 82%. In total, 180 LN fields were analysed. In the LN-region-based analysis, the sensitivity of 68Ga-PSMA PET/CT for detection of LNMs was 56%, the specificity was 98%, the PPV was 90% and the NPV was 94%. The mean size of missed LNMs was 2.7 mm. Receiver-operating characteristic curve analysis showed a high accuracy of maximum standardized uptake value (SUV In patients with intermediate- to high-risk PCa, 68Ga-PSMA PET/CT had a high specificity and a moderate sensitivity for LNM detection. 68Ga-PSMA PET/CT had the potential to replace current imaging for LN staging of patients with PCa scheduled for RP.

Step-by-Step Technique for Irreversible Electroporation of Focal Prostate Cancer: An Instructional Video Guide

Publisher: Elsevier BV

Date: 04-2016

DOI: 10.1016/J.JVIR.2016.01.003

Abstract: Focal therapy has emerged as a tissue-sparing treatment modality for selected men with low to intermediate volume, localized prostate cancer with the advantage of reducing treatment morbidity because of preservation of untreated prostate tissue and surrounding structures. Irreversible electroporation is an emerging interventional focal therapy modality that uses high voltage electrical fields to induce cell death. This instructional video guide (Fig) serves as an easy-to-understand, comprehensive educational tool so that a broader audience can gain an understanding of the techniques involved in this treatment modality.

Immunohistochemical Level of Unsulfated Chondroitin Disaccharides in the Cancer Stroma Is an Independent Predictor of Prostate Cancer Relapse

Publisher: American Association for Cancer Research (AACR)

Date: 09-2008

DOI: 10.1158/1055-9965.EPI-08-0204

Abstract: The glycosaminoglycan chondroitin sulfate is significantly increased in the peritumoral stroma of prostate tumors compared with normal stroma and is an independent predictor of prostate-specific antigen (PSA) relapse following radical prostatectomy. In this study, we determined whether specific alterations in the sulfation pattern of glycosaminoglycan chains in clinically organ-confined prostate cancer are associated with PSA relapse. Immunoreactivity to distinct glycosaminoglycan disaccharide epitopes was assessed by manually scoring the staining intensity in prostate tissues from patients with benign prostatic hyperplasia (n = 19), early-stage cancer (cohort 1, n = 55 and cohort 2, n = 275), and advanced-stage cancer (n = 20). Alterations to glycosaminoglycans in benign and malignant prostate tissues were determined by cellulose acetate chromatography and high-pressure liquid chromatography. Glycosaminoglycan disaccharide epitopes were localized to the peritumoral stroma of clinically localized prostate cancer. The level of immunostaining for unsulfated disaccharides (C0S) in the peritumoral stroma, but not for 4-sulfated (C4S) or 6-sulfated disaccharides (C6S), was significantly associated with the rate of PSA relapse following radical prostatectomy. High levels of C0S immunostaining were determined to be an independent predictor of PSA relapse (1.6-fold, P = 0.020). Advanced-stage prostate cancer tissues exhibited reduced electrophoretic mobility for chondroitin sulfate and increased unsulfated disaccharides when compared with benign prostatic hyperplasia tissues, whereas the sulfated disaccharide levels were unaffected. The level of C0S immunostaining in the peritumoral stroma is an independent determinant of PSA failure in clinically localized prostate cancer. Specific alterations to chondroitin sulfate side chains occurring during tumor development may be a crucial step for disease progression in prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008 (9):2488–97)

Treatment Outcomes from 68Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET.

Publisher: Society of Nuclear Medicine

Date: 26-07-2017

DOI: 10.2967/JNUMED.117.196683

Superior Biochemical Recurrence and Long-term Quality-of-life Outcomes Are Achievable with Robotic Radical Prostatectomy After a Long Learning Curve-Updated Analysis of a Prospective Single-surgeon Cohort of 2206 Consecutive Cases.

Publisher: Elsevier BV

Date: 05-2017

DOI: 10.1016/J.EURURO.2017.11.035

Abstract: Our earlier analysis suggested that robot-assisted radical prostatectomy (RARP) achieved superiority over open radical prostatectomy (ORP) in terms of positive surgical margin (PSM) rates and functional outcomes. With larger s le size and longer follow-up, the objective of this study update is to assess whether our previous findings are upheld and whether the improved PSM rates for RARP after an initial learning curve compared with ORP-as observed in our earlier analysis-ultimately resulted in improved biochemical control. Prospective observational study comparing two surgical techniques 2271 consecutive men underwent RARP (1520) or ORP (751) at a single centre from 2006 to 2016. Demographic and clinicopathological data were prospectively collected. The EPIC-QOL questionnaire was administered at baseline and 1.5, 3, 6, 12, and 24 mo. Multivariate linear regression modelled the difference in quality of life (QOL) domains against case number logistic and Cox regression modelled the differences in PSM and biochemical recurrence (BCR) hazard ratios (HR), respectively. A total of 2206 men were included in BCR/PSM analysis and 1045 consented for QOL analysis. Superior pT2 surgical margins, early and late sexual outcomes, and early urinary outcomes were upheld and became more robust (narrowing of 95% confidence intervals [CIs]). The risk of BCR was initially higher for RARP, improved after 191 RARPs, and was 35% lower (hazard ratio [HR] 0.65, 95% CI 0.47-0.90) at final RARP, plateauing after 226 RARPs. Improved late (12-24 mo) urinary bother scores (adjusted mean difference [AMD]=4.7, 95% CI 1.3-8.0) and irritative-obstructive scores (AMD=3.8, 95% CI 0.9-5.6) at final RARP were demonstrated. Limitations include observational single surgeon data, possible residual confounding, and short follow-up. The results from this updated analysis demonstrate that RARP can be beneficial for patients of high-volume surgeons, although more randomised studies and studies with survival outcomes are needed. Robot-assisted radical prostatectomy was able to improve functional and oncological outcomes in this single surgeon's learning curve.

Tumor volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over‐treatment

Publisher: Wiley

Date: 18-08-2015

DOI: 10.1002/PROS.23062

Abstract: There are conflicting results in the literature regarding the tumor volume (TV) threshold that defines insignificant prostate cancer (PCa). In this study, we retrospectively evaluate the association of an increasing TV with biochemical recurrence (BCR) following radical prostatectomy (RP) in order to provide further clarification surrounding the TV threshold definition for insignificant PCa. RP patients were recruited from January 2004 to December 2009. Inclusion criteria were localized (stage ≤pT2c, negative surgical margins) Gleason 6 PCa with a total TV of ≤2.50 cm(3) . BCR was the primary outcome and defined as a PSA of ≥0.1. All cases with BCR were re-evaluated by the pathologist with reassessment of tumor grade, pathological stage and surgical margin status. From 1,636 patients, 178 men (10.9%) met all inclusion criteria. Ninety-six patients (53.9%) had a TV <0.5 cm(3) and 82 patients (46.1%) had a TV 0.5-2.5 cm(3) . Three out of 178 patients (1.7%) presented with BCR during follow-up. One of these had TV <0.5 cm(3) and two had TV 0.5-2.5 cm(3) . These three cases of BCR underwent re-review of pathology one patient was found to have a positive surgical margin and one patient was upgraded to Gleason 3 + 4 = 7. The third patient was re-reported as having positive margins for a benign hyperplastic nodule (incomplete RP specimen). Subsequently, these three cases were excluded from final analysis as they did not fit inclusion criteria. Median follow-up duration was 84 months (IQR 70-102 months). On final analysis, there were no patients with BCR, corresponding with a final BCR rate of 0% for both patients with a TV of <0.5 cm(3) and 0.5-2.5 cm(3) . Our results have shown that, with a median follow-up of 84 (IQR 70-102) months, patients in our cohort with localized Gleason 6 PCa with a total TV 0.5-2.5 cm(3) have a BCR rate of 0%. We would support a more liberal total TV threshold of 2.5 cm(3) for the further development of algorithms to identify patients suitable for active surveillance.

Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development

Publisher: American Association for Cancer Research (AACR)

Date: 10-2010

DOI: 10.1158/1055-9965.EPI-10-0555

Abstract: Background: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis. Methods: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions. Results: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P & 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P & 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort. Conclusions: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis. Impact: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover, testing for aberrant expression of epigenetic genes such as those identified in this study may be beneficial in predicting in idual patient response to epigenetic therapies. Cancer Epidemiol Biomarkers Prev 19(10) 2611–22. ©2010 AACR.

Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer.

Publisher: Wiley

Date: 23-10-2014

DOI: 10.1111/BJU.12858

Abstract: To assess, in men undergoing active surveillance (AS) for low-risk prostate cancer, whether saturation or transperineal biopsy altered oncological outcomes, compared with standard transrectal biopsy. Retrospective analysis of prospectively collected data from two cohorts with localised prostate cancer (1998-2012) undergoing AS. Prostate cancer-specific, metastasis-free and treatment-free survival, unfavourable disease and significant cancer at radical prostatectomy (RP) were compared for standard ( 12 core, median 16), and transrectal vs transperineal biopsy, using multivariate analysis. In all, 650 men were included in the analysis with a median (mean) follow-up of 55 (67) months. Prostate cancer-specific, metastasis-free and biochemical recurrence-free survival were 100%, 100% and 99% respectively. Radical treatment-free survival at 5 and 10 years were 57% and 45% respectively (median time to treatment 7.5 years). On Kaplan-Meier analysis, saturation biopsy was associated with increased objective biopsy progression requiring treatment (log-rank P = 0.01). On multivariate Cox proportional hazards analysis, saturation biopsy (hazard ratio 1.68, P < 0.01) but not transperineal approach (P = 0.89) was associated with increased objective biopsy progression requiring treatment. On logistic regression analysis of 179 men who underwent RP for objective progression, transperineal biopsy was associated with lower likelihood of unfavourable RP pathology (odds ratio 0.42, P = 0.03) but saturation biopsy did not alter the likelihood (P = 0.25). Neither transperineal nor saturation biopsy altered the likelihood of significant vs insignificant cancer at RP (P = 0.19 and P = 0.41, respectively). AS achieved satisfactory oncological outcomes. Saturation biopsy increased progression to treatment on AS longer follow-up is needed to determine if this represents beneficial earlier detection of significant disease or over-treatment. Transperineal biopsy reduced the likelihood of unfavourable disease at RP, possibly due to earlier detection of anterior tumours.

Informed prostate cancer risk‐adjusted testing: a new paradigm

Publisher: Wiley

Date: 29-11-2012

DOI: 10.1111/J.1464-410X.2012.11621.X

Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 02-09-2014

DOI: 10.1038/PCAN.2014.33

Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross‐sectional study of the additive diagnostic value of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer

Publisher: Wiley

Date: 12-02-2020

DOI: 10.1111/BJU.14999

Abstract: Primary objectives: To determine the additive value of gallium‐68 prostate‐specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI‐RADS ≥3) but negative PSMA‐PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA‐PET/CT or only by systematic prostate biopsy to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA‐PET/CT to assess whether there may be health economic benefit or harm if PSMA‐PET/CT is incorporated into the diagnostic algorithm and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. The PRIMARY trial is a multicentre, prospective, cross‐sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic‐only) PSMA‐PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA‐PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA‐PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA‐PET/CT will be blinded to each other. The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA‐PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA‐PET/CT into the diagnostic algorithm. This trial will provide robust prospective data to determine the diagnostic ability of PSMA‐PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

Editorial Comment

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 03-2017

DOI: 10.1016/J.JURO.2016.09.137

Distribution of prostate cancer recurrences on gallium‐68 prostate‐specific membrane antigen (⁶⁸Ga‐PSMA) positron‐emission/computed tomography after radical prostatectomy with pathological

Publisher: Wiley

Date: 23-04-2020

DOI: 10.1111/BJU.15052

(68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment.

Publisher: Wiley

Date: 24-01-2016

DOI: 10.1111/BJU.13397

Abstract: To examine the detection rates of (68) Ga-PSMA-positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management. A total of 300 consecutive patients with prostate cancer (PCa) who underwent (68) Ga-PSMA-PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan-I) database. For the present analysis, we included patients with BCR (prostate-specific antigen [PSA] level ≥0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito-Urinary Group (FROGG) guidelines. Two readers assessed each (68) Ga-PSMA-PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological (68) Ga-PSMA uptake was investigated, and detection rates were determined according to PSA level. A total of 70 patients were included, and 53 positive (68) Ga-PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05-0.09 ng/mL, 8% were definitely positive the corresponding percentages for the other PSA ranges were as follows: PSA 0.1-0.19 ng/mL, 23% PSA 0.2-0.29 ng/mL, 58% PSA 0.3-0.49 ng/mL, 36% and PSA 0.5-0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological (68) Ga-PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the (68) Ga-PSMA findings there was a major management change in 20 (28.6%) patients. (68) Ga-PSMA appears to be useful for re-staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to (68) Ga-PSMA findings.

How Does Age Affect Urinary Continence following Robot-Assisted Radical Prostatectomy? A Prospective Multi-Institutional Study Using Independently Collected, Validated Questionnaires

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2022

DOI: 10.1097/JU.0000000000002391

Imaging: MRI improves cost and accuracy of prostate cancer biopsy.

Publisher: Springer Science and Business Media LLC

Date: 08-11-2017

DOI: 10.1038/NRUROL.2017.185

Survival gains needed to offset persistent adverse treatment effects in localised prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 24-01-2012

DOI: 10.1038/BJC.2011.552

Évaluation de la qualité de vie suite aux traitements actuels du cancer de prostate localisé

Publisher: Elsevier BV

Date: 11-2013

DOI: 10.1016/J.PUROL.2013.08.187

Salvage robot-assisted radical prostatectomy following focal ablation with irreversible electroporation: feasibility, oncological and functional outcomes

Publisher: Springer Science and Business Media LLC

Date: 02-03-2022

DOI: 10.1186/S12894-022-00978-W

Abstract: To report the feasibility, oncological and functional outcomes of salvage robot-assisted radical prostatectomy (sRARP) for recurrent prostate cancer (PCa) after irreversible electroporation (IRE). This was a retrospective analysis of patients who underwent sRARP by a single high-volume surgeon after IRE treatment in our institution. Surgical complications, oncological and functional outcomes were assessed. 15 patients with at least 12 months follow up were identified out of the 234 men who underwent primary IRE between 2013 and 2019. The median [IQR] age was 68 (62–70) years. The median [IQR] time from focal IRE to sRARP was 42 (21–57) months. There were no rectal, bladder or ureteric injuries. The T-stage was pT2 in 9 (60%) patients and pT3a in 6 (40%) patients. Only one (7%) patient had a positive surgical margin. At a median [IQR] follow up of 22 (16–32) months no patient had a biochemical recurrence (PSA 0.2). All 15 patients were continent (pad-free) by 6 months and 9 (60%) patients had erections sufficient for intercourse with or without PDE5 inhibitors. No predisposing factors were identified for predicting erectile dysfunction after sRARP. In patients with recurrent or residual significant PCa after focal IRE ablation it is feasible to obtain good functional and oncological outcomes with sRARP. Our results demonstrate that good outcomes can be achieved with sRARP, when respecting close monitoring post-IRE, good patient selection and surgical experience. The limitations of this study are that it is a small series, with short follow up and a lack of standardised quality of life instruments.

Prognostic impact of positive surgical margins in surgically treated prostate cancer: Multi-institutional assessment of 5831 patients

Publisher: Elsevier BV

Date: 12-2005

DOI: 10.1016/J.UROLOGY.2005.06.108

Abstract: To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables. We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records. In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P < 0.001). The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.

Diagnostic accuracy of multi-parametric MRI and transrectal ultrasound-guided biopsy in prostate cancer.

Publisher: Elsevier BV

Date: 02-2017

DOI: 10.1016/S0140-6736(17)30121-6

Radiomic features for prostate cancer detection on MRI differ between the transition and peripheral zones: Preliminary findings from a multi‐institutional study

Publisher: Wiley

Date: 19-12-2016

DOI: 10.1002/JMRI.25562

High prostate‐specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI‐RADS score 4 or 5 confers a high probability of

Publisher: Wiley

Date: 20-04-2022

DOI: 10.1111/BJU.15736

ABSTRACTS

Publisher: Wiley

Date: 14-01-2010

DOI: 10.1111/J.1464-410X.2010.09122.X

Expression of E6AP and PML predicts for prostate cancer progression and cancer-specific death.

Publisher: Elsevier BV

Date: 12-2014

DOI: 10.1093/ANNONC/MDU454

Abstract: The promyelocytic leukemia (PML) tumor suppressor plays an important role in the response to a variety of cellular stressors and its expression is downregulated or lost in a range of human tumors. We have previously shown that the E3 ligase E6-associated protein (E6AP) is an important regulator of PML protein stability but the relationship and clinical impact of PML and E6AP expression in prostatic carcinoma is unknown. E6AP and PML expression was assessed in tissue microarrays from a phase I discovery cohort of 170 patients treated by radical prostatectomy for localized prostate cancer (PC). Correlation analysis was carried out between PML and E6AP expression and clinicopathological variates including PSA as a surrogate of disease recurrence. The results were confirmed in a phase II validation cohort of 318 patients with associated clinical recurrence and survival data. Survival analysis of the phase I cohort revealed that patients whose tumors showed reduced PML and high E6AP expression had reduced time to PSA relapse (P = 0.012). This was confirmed in the phase II validation cohort where the expression profile of high E6AP/low PML was significantly associated with reduced time to PSA relapse (P < 0.001), clinical relapse (P = 0.016) and PC-specific death (P = 0.014). In multivariate analysis, this expression profile was an independent prognostic indicator of PSA relapse and clinical relapse independent of clinicopathologic factors predicting recurrence. This study identifies E6AP and PML as potential prognostic markers in localized prostate carcinoma and supports a role for E6AP in driving the downregulation or loss of PML expression in prostate carcinomas.

Impact on genitourinary function and quality of life following focal irreversible electroporation of different prostate segments

Publisher: Galenos Yayinevi

Date: 06-09-2018

DOI: 10.5152/DIR.2018.17374

Selection of patients for nerve sparing surgery in robot‐assisted radical prostatectomy

Publisher: Wiley

Date: 09-11-2021

DOI: 10.1002/BCO2.115

Abstract: Robot‐assisted radical prostatectomy (RARP) has become the standard surgical procedure for localized prostate‐cancer (PCa). Nerve‐sparing surgery (NSS) during RARP has been associated with improved erectile function and continence rates after surgery. However, it remains unclear what are the most appropriate indications for NSS. The objective of this study is to systematically review the available parameters for selection of patients for NSS. The weight of different clinical variables, multiparametric magnetic‐resonance‐imaging (mpMRI) findings, and the impact of multiparametric‐nomograms in the decision‐making process on (side‐specific) NSS were assessed. This systematic review searched relevant databases and included studies performed from January 2000 until December 2020 and recruited a total of 15 840 PCa patients. Studies were assessed that defined criteria for (side‐specific) NSS and associated them with oncological safety and/or functional outcomes. Risk of bias assessment was performed. Nineteen articles were eligible for full‐text review. NSS is primarily recommended in men with adequate erectile function, and with low‐risk of extracapsular extension (ECE) on the side‐of NSS. Separate clinical and radiological variables have low accuracy for predicting ECE, whereas nomograms optimize the risk‐stratification and decision‐making process to perform or to refrain from NSS when oncological safety (organ‐confined disease, PSM rates) and functional outcomes (erectile function and continence rates) were assessed. Consensus exists that patients who are at high risk of ECE should refrain from NSS. Several multiparametric preoperative nomograms were developed to predict ECE with increased accuracy compared with single clinical, pathological, or radiological variables, but controversy exists on risk thresholds and decision rules on a conservative versus a less‐conservative surgical approach. An in idual clinical judgment on the possibilities of NSS set against the risks of ECE is warranted. NSS is aimed at sparing the nerves responsible for erection. NSS may lead to unfavorable tumor control if the risk of capsule penetration is high. Nomograms predicting extraprostatic tumor‐growth are probably most helpful.

The PRIMARY Score: Using intra-prostatic PSMA PET/CT patterns to optimise prostate cancer diagnosis.

Publisher: Society of Nuclear Medicine

Date: 17-03-2022

DOI: 10.2967/JNUMED.121.263448

HSD17B4 overexpression, an independent biomarker of poor patient outcome in prostate cancer.

Publisher: Elsevier BV

Date: 03-2008

DOI: 10.1016/J.MCE.2008.11.021

Abstract: Steroid hormones and their metabolising enzymes have been studied extensively for their potential role in prostate cancer, with more recent interest in the androgen/estrogen inactivating enzyme 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4). Gene expression profiling showed HSD17B4 to be significantly overexpressed in prostate cancer compared to matched-benign epithelium. We therefore hypothesized that altered HSD17B4 expression may contribute to prostate cancer progression via altered hormone balance. In this study, HSD17B4 mRNA and protein expression were assessed by in situ hybridisation (ISH) and immunohistochemistry (IHC), respectively, in tissue arrays of prostate tissue from 172 patients treated by radical prostatectomy. Overexpression of HSD17B4 mRNA and protein was associated with prostate cancer (P<0.0001) and multivariate Cox proportional hazards analysis, adjusted for known prognostic indicators, demonstrated HSD17B4 mRNA and high protein expression were significant independent predictors of poor patient outcome as measured by time until PSA relapse (mRNA: hazards ratio [HR]=1.90, 95% confidence interval [CI]=1.15-3.12 P<0.0001 and protein: HR=2.09, 95% CI=1.31-3.33 P=0.0026). Here we provide strong evidence that both mRNA and protein overexpression of HSD17B4 is not only associated with the presence of prostate cancer, but is also a significant independent predictor of poor patient outcome.

The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis

Publisher: MDPI AG

Date: 07-05-2020

DOI: 10.3390/CANCERS12051178

Abstract: Background: While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to in idualize treatment. Methods: Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour s les were derived from prostate, lymph nodes, bone and brain. Results: Most s les had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy (LRP1B, CDK12, MLH1) and one patient had germline and somatic BRCA2 alterations. Conclusions: Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in in idual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an in idual’s molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an in idual at any stage of the disease.

Circulating microRNAs predict biochemical recurrence in prostate cancer patients

Publisher: Springer Science and Business Media LLC

Date: 11-07-2013

DOI: 10.1038/BJC.2013.369

Mutational load of the mitochondrial genome predicts pathological features and biochemical recurrence in prostate cancer

Publisher: Impact Journals, LLC

Date: 05-10-2016

DOI: 10.18632/AGING.101044

Identifying the morphologic basis for radiomic features in distinguishing different Gleason grades of prostate cancer on MRI: Preliminary findings

Publisher: Public Library of Science (PLoS)

Date: 31-08-2018

DOI: 10.1371/JOURNAL.PONE.0200730

A Multinational, Multi-institutional Study Comparing Positive Surgical Margin Rates Among 22 393 Open, Laparoscopic, and Robot-assisted Radical Prostatectomy Patients

Publisher: Elsevier BV

Date: 09-2014

DOI: 10.1016/J.EURURO.2013.11.018

Abstract: Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and volume. To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates. Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011. The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort. Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%) significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature missing data across covariates, especially year of surgery in many of the open cohort cases lack of standardized histologic processing and central pathology review and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and in idual surgeon caseload. This multinational, multi-institutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases. In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.

Location and Pathological Characteristics of Cancers in Radical Prostatectomy Specimens Identified by Transperineal Biopsy Compared to Transrectal Biopsy

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-2012

DOI: 10.1016/J.JURO.2012.05.006

Abstract: Anterior tumors are estimated to constitute 20% of prostate cancers. Current data indicate that transperineal biopsy is more reliable than transrectal biopsy in identifying these tumors. If correct, this superior reliability should result in an increased proportion of anterior tumors identified by transperineal biopsy. We investigated this hypothesis with reference to prostatectomy specimens. Radical prostatectomy histopathology records were retrospectively examined. Patients were grouped based on primary transperineal or transrectal biopsy as the modality used to identify the initial cancer. After grouping, tumor location and size were recorded and, thus, the proportion of anterior tumors was determined. A total of 1,132 (414 transperineal and 718 transrectal) prostatectomy specimens were examined. Overall mean tumor size (1.8 and 2.0 cm(3)), stage (pT2 63.3% and 61%) and significance (5.1% and 5.1%) for the transperineal and transrectal methods were similar. However, the transperineal method was associated with proportionally more anterior tumors (16.2% vs 12%, p = 0.046), and identified them at a smaller size (1.4 vs 2.1 cm(3), p = 0.03) and lower stage (extracapsular extension 13% vs 28%, p = 0.03) compared to the transrectal method. The pT3 positive surgical margin rate for anterior vs other tumors was 69% vs 34.9%, respectively. Overall transrectal and transperineal biopsy identify cancers that are similar in size, stage and significance. However, transperineal biopsy detected proportionally more anterior tumors (16.2% vs 12%), and identified them at a smaller size (1.4 vs 2.1 cm(3)) and stage (extracapsular extension 13% vs 28%) compared to transrectal biopsy. Identifying anterior tumors early is important because the positive surgical margin rate for anterior pT3 lesions is significantly higher.

Combination of Peri-Tumoral and Intra-Tumoral Radiomic Features on Bi-Parametric MRI Accurately Stratifies Prostate Cancer Risk: A Multi-Site Study

Publisher: MDPI AG

Date: 06-08-2020

DOI: 10.3390/CANCERS12082200

Abstract: Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D’Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) high-risk (L-vs.-H), and (2) (intermediate- and high-risk (L-vs.-I + H)) lesions were identified. Using a multi-institutional training cohort of 151 lesions (D1, N = 116 patients), machine learning classifiers were trained using peri- and intra-tumoral features in idually and in combination. The remaining 150 lesions (D2, N = 115 patients) were used for independent hold-out validation and were evaluated using Receiver Operating Characteristic (ROC) analysis and compared with PI-RADS v2 scores. Results: Validation on D2 using peri-tumoral radiomics alone resulted in areas under the ROC curve (AUCs) of 0.84 and 0.73 for the L-vs.-H and L-vs.-I + H classifications, respectively. The best combination of intra- and peri-tumoral features resulted in AUCs of 0.87 and 0.75 for the L-vs.-H and L-vs.-I + H classifications, respectively. This combination improved the risk stratification results by 3–6% compared to intra-tumoral features alone. Our radiomics-based model resulted in a 53% accuracy in differentiating L-vs.-H compared to PI-RADS v2 (48%), on the validation set. Conclusion: Our findings suggest that peri-tumoral radiomic features derived from prostate bi-parametric MRI add independent predictive value to intra-tumoral radiomic features for PCa risk assessment.

Results of a Prospective Phase 2 Pilot Trial of 177Lu-PSMA-617 Therapy for Metastatic Castration-Resistant Prostate Cancer Including Imaging Predictors of Treatment Response and Patterns of Progression.

Publisher: Elsevier BV

Date: 02-2018

DOI: 10.1016/J.CLGC.2018.09.014

Abstract: Men with progressive, symptomatic metastatic castration-resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane-based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P < .007), and PSMA SUV mean 6 ± 4 versus 10 ± 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted ≥ 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression. PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options.

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations

Publisher: Wiley

Date: 22-06-2018

DOI: 10.1111/BJU.14412

Stage migration in localized prostate cancer has no effect on the post‐radical prostatectomy Kattan nomogram

Publisher: Wiley

Date: 11-02-2010

DOI: 10.1111/J.1464-410X.2009.08842.X

Extraprostatic extension (EPE) of prostatic carcinoma: is its proximity to the surgical margin or Gleason score important?

Publisher: Wiley

Date: 15-12-2014

DOI: 10.1111/BJU.12911

Abstract: To examine the association between histopathological factors of extraprostatic prostate cancer and outcome. Patients with extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph node involvement were analysed from a consecutive radical prostatectomy cohort of 1136 (2002-2006) for: (i) distance of EPE from the margin (ii) Gleason score of the EPE and (iii) extent of EPE. Log-rank, Kaplan-Meier, and Cox regression analyses were performed. The study included 194 pT3a, pN0, R0 patients with a median follow-up of 5.4 years, with 37 (19%) patients experiencing biochemical relapse (BCR). On univariable analysis, patients with a Gleason score of ≥8 in the extraprostatic portion showed increased incidence of BCR compared with those with Gleason scores of ≤7 (P = 0.03). The proximity of the EPE to the margin (0.01-7.5 mm) did not correlate with BCR. On multivariable analysis, the extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did not correlate with BCR. Data from this study using current International Society of Urological Pathology Gleason scoring and EPE criteria indicate that close proximity of EPE to the margin is not associated with recurrence. Gleason score ≥8 within EPE is associated with an increased BCR risk on univariable analysis, but larger studies are required to confirm whether extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise overall Gleason score 7 cancer.

p53 nuclear accumulation as an early indicator of lethal prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 21-08-2019

DOI: 10.1038/S41416-019-0549-8

Effect of FAK inhibitor VS-6063 (defactinib) on docetaxel efficacy in prostate cancer

Publisher: Wiley

Date: 05-01-2018

DOI: 10.1002/PROS.23476

Abstract: Docetaxel, the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration-sensitive prostate cancer (CSPC) when combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models. Docetaxel-resistant CRPC cells, mice with PC3 xenografts, and ex vivo cultures of patient-derived primary prostate tumors were treated with VS-6063 and/or docetaxel, or vehicle control. Cell counting, immunoblotting, and immunohistochemistry techniques were used to evaluate the treatment effects. Docetaxel and VS-6063 co-treatment caused a greater decrease in the viability of docetaxel-resistant CRPC cells, and a greater inhibition in PC3 xenograft growth compared to either monotherapy. FAK expression in human primary prostate cancer was positively associated with advanced tumor stage. Patient-derived prostate tumor explants cultured with both docetaxel and VS-6063 displayed a higher percentage of apoptosis in cancer cells, than monotherapy treatment. Our findings suggest that co-administration of the FAK inhibitor, VS-6063, with docetaxel represents a potential therapeutic strategy to overcome docetaxel resistance in prostate cancer.

Loss of AZGP1 as a Superior Predictor of Relapse in Margin-Positive Localized Prostate Cancer

Publisher: Wiley

Date: 30-07-2016

DOI: 10.1002/PROS.23233

Abstract: Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs. Our study aimed to determine whether the biomarkers AZGP1 expression and Gleason grade at the site of a PSM are significant independent markers of biochemical and clinical relapse (CR) when modeled together and whether one of these biomarkers may be superior in its capacity to predict outcome. A cohort of 275 consecutive patients with margin-positive localized PC following surgery were assessed for Gleason grade and AZGP1 expression at the PSM. BR-free survival was the primary end-point, while CR-free survival and PC-specific death were secondary endpoints. Kaplan-Meier Analysis and Cox Proportional Hazards Modeling were performed. Absent AZGP1 expression was significantly associated with increased risk of BR (P = 0.001) and PC-specific death (P = 0.02). Gleason grade ≥4 at PSM was associated with BR (P = 0.02), CR (P = 0.003), and PC-specific death (P = 0.004). On multivariable analysis, absent AZGP1 expression remained an independent predictor of BR (HR 2.4, 95%CI 1.5-3.9, P < 0.001) when modeled with Gleason grade at margin (HR 1.3, 95%CI 0.9-1.9, P = 0.16), preoperative PSA (P = 0.002), seminal vesicle involvement (P = 0.002), extraprostatic extension (P = 0.001), Gleason score (P = 0.01), adjuvant treatment (P = 0.75), linear length of the involved margin (P = 0.001) and margin number (P = 0.09). Absent AZGP1 expression is an independent predictor of BR in margin-positive localized PC and is associated with increased PC-specific mortality in a Phase II study. Absent AZGP1 expression was superior to Gleason grade at PSM in predicting relapse and should be incorporated into subsequent clinical trials of post-operative radiotherapy in men with margin-positive PC. Prostate 76:1491-1500, 2016. © 2016 Wiley Periodicals, Inc.

Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer following radical prostatectomy

Publisher: Oxford University Press (OUP)

Date: 04-10-2006

DOI: 10.1093/JNCI/DJJ378

Abstract: The risk of metastatic progression for prostate cancer patients who undergo radical prostatectomy is best estimated presently based on prostate-specific antigen (PSA) doubling time (PSADT). However, additional markers of risk are needed to identify patients who may benefit from aggressive salvage treatment. A decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate epithelium was previously shown to predict biochemical recurrence, as defined by rising levels of serum PSA after radical prostatectomy. We assessed the reliability with which AZPG1 expression could predict clinical recurrence and metastatic progression. Using immunohistochemical methods, we analyzed AZPG1 expression in malignant prostate epithelium in prostatectomy specimens from 228 prostate cancer patients. Low (i.e., absent or weak) AZGP1 expression was associated with clinical recurrence (defined as confirmed localized recurrence, metastasis, or death from prostate cancer hazard ratio [HR] = 4.8, 95% confidence interval [CI] = 2.2 to 10.7, P<.001) and with bony metastases or death from prostate cancer (HR = 8.0, 95% CI = 2.6 to 24.3, P<.001). Among the 17 patients in the cohort in whom clinical recurrence was associated with short PSADT, absent or weak AZGP1 expression was observed in 13 patients. If these preliminary findings are validated in independent cohorts, the measurement of AZGP1 levels in radical prostatectomy specimens may permit an accurate and timely assessment of risk of metastatic progression after radical prostatectomy.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2015

DOI: 10.1016/J.JURO.2015.10.140

Abstract: We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of in idual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

Androgen regulation of multidrug resistance-associated protein 4 (MRP4/ABCC4) in prostate cancer.

Publisher: Wiley

Date: 15-09-2008

DOI: 10.1002/PROS.20809

Abstract: MRP4/ABCC4 is an ATP-binding cassette transporter expressed in normal prostate. This study aimed to define the pattern of MRP4/ABCC4 expression in normal and malignant prostate tissue and the relationship of MRP4/ABCC4 expression and function in response to androgen signaling. Eighty-four radical prostatectomy specimens from patients with localized prostate cancer (PC) (22 neoadjuvant androgen ablation, AA, 62 no AA), 42 non-cancer and 16 advanced PCs were assessed for MRP4/ABCC4 mRNA rotein expression. The effect of DHT and bicalutamide on LNCaP cells was assessed by immunoblotting. HEK293 cells (+/-MRP4/ABCC4) were assessed for the ability to efflux androgens and anti-androgens. MRP4/ABCC4 mRNA rotein levels were higher in localized PC compared to non-cancer (P = 0.006). MRP4/ABCC4 levels were significantly decreased in PCs treated with AA compared to cancers exposed to normal testosterone levels (P < 0.0001). MRP4/ABCC4 expression in normal human tissues was limited to the prostate and the renal tubules. MRP4/ABCC4 protein levels increased in LNCaP cells after DHT which was partially blocked by bicalutamide. However, DHT did not alter the activation of the MRP4/ABCC4 promotor in luciferase reporter assays and testosterone, DHT, flutamide and hydroxy-flutamide were not substrates for MRP4/ABCC4. Elevated MRP4/ABCC4 expression is found in malignant compared to benign prostate tissue while lower MRP4/ABCC4 expression is seen after AA. Furthermore, MRP4/ABCC4 is upregulated by androgen and downregulated by anti-androgen treatment in vitro potentially through an indirect mode of action. These data strongly suggest that MRP4/ABCC4 is an androgen-regulated gene important in the progression to PC and may be a potential drug target.

The Impact of 68Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study.

Publisher: Society of Nuclear Medicine

Date: 23-06-2017

DOI: 10.2967/JNUMED.117.197160

MRI improves active surveillance of prostate cancer however biopsy is still crucial.

Publisher: Wiley

Date: 08-2018

DOI: 10.1111/BJU.14424

Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer.

Publisher: Wiley

Date: 13-05-2022

DOI: 10.1111/BJU.15759

Abstract: To evaluate: (i) safety, (ii) feasibility, and medium-term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE). An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life. In four participating centres, a total of 39 patients with a median (interquartile range [IQR]) age 64 (60-67) years were identified. No serious adverse events occurred during or following sRP and surgery was deemed feasible without difficulties. The median (IQR) time to recurrence following IRE was 14.3 (9.1-38.8) months. Pathology results showed localised disease in 21 patients (53.8%) and locally-advanced disease in 18 (46.2%). Positive surgical margins (PSMs) were observed in 10 patients (25.6%), of which six (15.4%) had significant PSMs. A persistent detectable prostate-specific antigen level was found in one case after sRP, caused by metastatic disease. One patient had a biochemical recurrence 6 months after sRP. These two cases, together with a PSM case, required additional therapy after sRP. After a median (IQR) follow-up of 17.7 (11.8-26.4) months, urinary continence and erectile function were preserved in 34 (94.4%) and 18 patients (52.9%), respectively, while quality of life remained stable. Salvage RP is safe and feasible for patients with recurrent localised PCa following initial IRE treatment. The medium-term oncological and functional outcomes are similar to primary RP. Strict patient selection for focal therapy and standardised follow-up is needed as some patients developed high-grade disease.

Prospective Comparison of ¹⁸F-Fluoromethylcholine Versus ⁶⁸Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Ta

Publisher: Society of Nuclear Medicine

Date: 25-06-2015

DOI: 10.2967/JNUMED.115.160382

Abstract: In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. (11)C-choline and (18)F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga-N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of (68)Ga-PSMA versus (18)F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy. A s le of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. (68)Ga-PSMA, (18)F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with (68)Ga-PSMA alone, 11 (42%) with both (18)F-fluoromethylcholine and (68)Ga-PSMA, and only 1 (4%) with (18)F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for (68)Ga-PSMA versus 12.5% for (18)F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for (68)Ga-PSMA versus 31% for (18)F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for (68)Ga-PSMA versus 57% for (18)F-fluoromethylcholine. On lesion-based analysis, (68)Ga-PSMA detected more lesions than (18)F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for (68)Ga-PSMA than for (18)F-fluoromethylcholine (28.6 for (68)Ga-PSMA vs. 9.4 for (18)F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to (68)Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 (68)Ga-PSMA-positive lesions were consistent with prostate cancer ((68)Ga-PSMA was true-positive). The lesion positive on (18)F-fluoromethylcholine imaging and negative on (68)Ga-PSMA imaging was shown at biopsy to be a false-positive (18)F-fluoromethylcholine finding ((68)Ga-PSMA was true-negative). In patients with biochemical failure and a low PSA level, (68)Ga-PSMA demonstrated a significantly higher detection rate than (18)F-fluoromethylcholine and a high overall impact on management.

Vroege oncologische uitkomsten van [68Ga]PSMA-PET/CT-gestuurde salvagetherapie bij mannen met biochemisch recidief na radicale prostatectomie

Publisher: Springer Science and Business Media LLC

Date: 25-07-2018

DOI: 10.1007/S13629-018-00215-W

Predictive value of the 2014 International Society of Urological Pathology grading system for prostate cancer in patients undergoing radical prostatectomy with long‐term follow‐up

Publisher: Wiley

Date: 30-04-2017

DOI: 10.1111/BJU.13857

Abstract: To assess the relationship between the International Society of Urological Pathology (ISUP) 2014 grading system, biochemical recurrence (BCR) and clinical recurrence (CLR) after radical prostatectomy (RP), to determine whether the 2014 ISUP grading system is a better predictor of survival compared with the previous Gleason scoring systems, and to investigate whether incorporation of the tertiary pattern/grade into the ISUP scoring system significantly improves its efficacy. A total of 635 RP cases (1991-1999) were identified from a database at a single institution. A histopathology review was performed to re-grade the cases as per the ISUP 2014 grading system. All relevant clinicopathological data and clinical follow-up (median [range] 15.25 [0.3-26] years) were obtained. Log-rank, Kaplan-Meier, Cox regression and Harrell's concordance c-indices analyses were performed. At a median follow-up of 15 years, 276 patients (44%) had BCR and 41 (7%) had CLR. Grade Groups 1, 2, 3, 4 and 5 were seen in 112 (18%), 307 (48%), 129 (20%), 33 (5%) and 54 patients (9%), respectively: 337 (53%) were upgraded, while 70 (11%) were downgraded compared with the 1992 Gleason system. Grade Group (hazard ratio [HR] 4.9 P < 0.001) and preoperative prostate-specific antigen (PSA) level (HR 1.4 P < 0.001) were independent predictors of BCR. Only Grade Group 5 (HR 12.3 P = 0.02), preoperative PSA (HR 1.6 P < 0.001), stage pT3b (HR 3.1 P = 0.03) and pT4 (HR 12.4 P < 0.001) independently predicted CLR. Harrell's c-indices showed that the 2014 ISUP grading system was a significantly better predictor of BCR and CLR as well as prostate cancer-specific death, compared with the 2005 ISUP modified Gleason system. The replacement of the secondary pattern by the tertiary pattern did not alter the prognostic efficacy of the ISUP 2014 grading system. The ISUP 2014 grading system is a significant independent predictor of both BCR and CLR, outperforming the 2005 ISUP modified Gleason system. This classification system has the potential to influence clinical decision-making after RP.

Use of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical

Publisher: Wiley

Date: 29-11-2019

DOI: 10.1111/BJU.14944

PSMA‐PET in Addition to mpMRI and Biopsies to Select Prostate Cancer Patients for Focal Therapy

Publisher: Wiley

Date: 19-10-2023

DOI: 10.1111/BJU.16207

Index grade group is superior to composite grade group for prediction of biochemical recurrence following radical prostatectomy

Publisher: Elsevier BV

Date: 06-2023

DOI: 10.1016/J.PATHOL.2022.10.012

AutoStitcher: An Automated Program for Efficient and Robust Reconstruction of Digitized Whole Histological Sections from Tissue Fragments

Publisher: Springer Science and Business Media LLC

Date: 26-07-2016

DOI: 10.1038/SREP29906

Abstract: In applications involving large tissue specimens that have been sectioned into smaller tissue fragments, manual reconstruction of a “pseudo whole-mount” histological section (PWMHS) can facilitate (a) pathological disease annotation and (b) image registration and correlation with radiological images. We have previously presented a program called HistoStitcher, which allows for more efficient manual reconstruction than general purpose image editing tools (such as Photoshop). However HistoStitcher is still manual and hence can be laborious and subjective, especially when doing large cohort studies. In this work we present AutoStitcher, a novel automated algorithm for reconstructing PWMHSs from digitized tissue fragments. AutoStitcher reconstructs (“stitches”) a PWMHS from a set of 4 fragments by optimizing a novel cost function that is domain-inspired to ensure (i) alignment of similar tissue regions and (ii) contiguity of the prostate boundary. The algorithm achieves computational efficiency by performing reconstruction in a multi-resolution hierarchy. Automated PWMHS reconstruction results (via AutoStitcher) were quantitatively and qualitatively compared to manual reconstructions obtained via HistoStitcher for 113 prostate pathology sections. Distances between corresponding fiducials placed on each of the automated and manual reconstruction results were between 2.7%–3.2%, reflecting their excellent visual similarity.

Focal ablation of apical prostate cancer lesions with irreversible electroporation (IRE)

Publisher: Springer Science and Business Media LLC

Date: 02-06-2020

DOI: 10.1007/S00345-020-03275-Z

Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?

Publisher: Wiley

Date: 27-09-2023

DOI: 10.1111/BJU.15883

Abstract: To provide a summary and discussion of international guidelines, position statements and consensus statements in relation to focal therapy (FT) for prostate cancer (PCa). The European Association of Urology‐European Association of Nuclear Medicine‐European Society for Radiotherapy and Oncology‐European Society of Urogential Radiology‐International Society of Urological Pathology‐International Society of Geriatric Oncology and American Urological Association‐American Society for Radiation Oncology‐Society of Urologic Oncology guidelines were interrogated for recommendations for FT. PubMed and Ovid Medline were searched for consensus statements. Only studies in English since 2015 were included. Reference lists of the included articles were also interrogated and a manual search for studies was also performed. Our results showed a lack of long‐term randomised data for FT. International Urological guidelines emphasised the need for more high‐quality clinical trials with robust oncological and toxicity outcomes. Consensus and positions statements were heterogenous. A globally accepted guideline for FT planning, technique and follow‐up are still yet to be determined. Well‐designed studies with long‐term follow‐up and robust clinical and toxicity endpoints are needed to improve our understanding of FT and create uniform guidelines to streamline management and follow‐up.

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Publisher: Wiley

Date: 28-06-2011

DOI: 10.1111/J.1464-410X.2011.10361.X

Diagnostic accuracy of

Publisher: Wiley

Date: 09-07-2019

DOI: 10.1111/BJU.14794

Abstract: To evaluate the ability of prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET)/computed tomography (CT) to detect intermediate-grade intra-prostatic prostate cancer (PCa), and to determine if PSMA-PET improves the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI). A total of 56 consecutive patients with International Society of Urological Pathology (ISUP) grade 2-3 PCa after radical prostatectomy, who underwent both mpMRI and PSMA-PET CT (hereafter PSMA-PET) preoperatively, were enrolled in this study. The accuracy of PSMA-PET, mpMRI alone, and the two procedures in combination was analysed for identifying ISUP grades 1-3 within a 12-segment model. The accuracy of a combined predictive model (PSMA-PET and mpMRI) was determined. Receiver-operating characteristic curve analysis to determine the optimal standardized uptake value (SUV On a per-patient basis, the sensitivities for PSMA-PET and mpMRI in identifying ISUP grades 2-3 PCa were 100% and 97%, respectively. Assessing ISUP grade ≥2 PCa using a 12-segment analysis, PSMA-PET demonstrated greater diagnostic accuracy (area under the curve), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), with values of 0.91, 88%, 93%, 95% and 85%, respectively, than did mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] 3-5), at 0.79, 68%, 91%, 87%, and 75%, respectively. When used in combination (PSMA-PET and mpMRI PIRADS 4-5), sensitivity, specificity, NPV and PPV were 92%, 90%, 96% and 81%, respectively. The sensitivity for both techniques reduced markedly when assessing ISUP grade 1 PCa (18% for PSMA-PET, 10% for mpMRI). An SUV PSMA-PET is accurate in detecting segments containing intermediate-grade intra-prostatic PCa (ISUP grade ≥ 2), compared with and complementary to mpMRI. By contrast the detection rate for ISUP grade 1 disease for both PSMA-PET and mpMRI was low.

Superior quality of life and improved surgical margins are achievable with robotic radical prostatectomy after a long learning curve: a prospective single-surgeon study of 1552 consecutive cases.

Publisher: Elsevier BV

Date: 03-2013

DOI: 10.1016/J.EURURO.2013.10.030

Abstract: Comparative studies suggest functional and perioperative superiority of robot-assisted radical prostatectomy (RARP) over open radical prostatectomy (ORP). To determine whether high-volume experienced open surgeons can improve their functional and oncologic outcomes with RARP and, if so, how many cases are required to surpass ORP outcomes and reach the learning curve plateau. A prospective observational study compared two surgical techniques: 1552 consecutive men underwent RARP (866) or ORP (686) at a single Australian hospital from 2006 to 2012, by one surgeon with 3000 prior ORPs. Demographic and clinicopathologic data were collected prospectively. The Expanded Prostate Cancer Index Composite quality of life (QoL) questionnaire was administered at baseline, 1.5, 3, 6, 12, and 24 mo. Multivariate linear and logistic regression modelled the difference in QoL domains and positive surgical margin (PSM) odds ratio (OR), respectively, against case number. A total of 1511 men were included in the PSM and 609 in the QoL analysis. RARP sexual function scores surpassed ORP scores after 99 RARPs and increased to a mean difference at 861st case of 11.0 points (95% confidence interval [CI], 5.9-16.1), plateauing around 600-700 RARPs. Early urinary incontinence scores for RARP surpassed ORP after 182 RARPs and increased to a mean difference of 8.4 points (95% CI, 2.1-14.7), plateauing around 700-800 RARPs. The odds of a pT2 PSM were initially higher for RARP but became lower after 108 RARPs and were 55% lower (OR: 0.45 95% CI, 0.22-0.92) by the 866th RARP. The odds of a pT3/4 PSM were initially higher for RARP but decreased, plateauing around 200-300 RARPs with an OR of 1.15 (0.68-1.95) at the 866th RARP. Limitations include single-surgeon data and residual confounding. RARP had a long learning curve with inferior outcomes initially, and then showed progressively superior sexual, early urinary, and pT2 PSM outcomes and similar pT3 PSM and late urinary outcomes. Learning RARP was worthwhile for this high-volume surgeon, but the learning curve may not be justifiable for late-career/low-volume surgeons further studies are needed.

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy

Publisher: Wiley

Date: 12-10-2012

DOI: 10.1111/J.1464-410X.2011.10572.X

EAU-EANM-ESTRO-ESUR-SIOG Prostate Cancer Guideline Panel Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETEC

Publisher: Elsevier BV

Date: 12-2019

DOI: 10.1016/J.EURURO.2019.09.020

Abstract: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised. To develop consensus statements for all domains of DAT. A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed. A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%) the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion. Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials. We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers.

Multiparametric magnetic resonance imaging guided diagnostic biopsy detects significant prostate cancer and could reduce unnecessary biopsies and over detection: A prospective study

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2014

DOI: 10.1016/J.JURO.2014.01.014

Abstract: Multiparametric magnetic resonance imaging appears to improve prostate cancer detection but prospective studies are lacking. We determined the accuracy of multiparametric magnetic resonance imaging for detecting significant prostate cancer before diagnostic biopsy in men with abnormal prostate specific antigen/digital rectal examination. In this single center, prospective study men older than 40 years with abnormal prostate specific antigen/digital rectal examination and no previous multiparametric magnetic resonance imaging underwent T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging without an endorectal coil. Imaging was allocated alternately to 1.5/3.0 Tesla. Imaging was double reported independently using PI-RADS (Prostate Imaging Reporting and Data System) by specialist radiologists. Transperineal grid directed 30-core biopsy was performed with additional magnetic resonance imaging directed cores for regions of interest outside template locations. Four significant cancer definitions were tested. Chi-square and logistic regression analysis was done. Men undergoing prostatectomy were analyzed. Of the 165 men who enrolled in the study 150 were analyzed. Median age was 62.4 years, median prostate specific antigen was 5.6 ng/ml, 29% of patients had an abnormal digital rectal examination and 88% underwent initial biopsy. Multiparametric magnetic resonance imaging was positive (PI-RADS 3 to 5) in 66% of patients, 61% had prostate cancer and 30% to 41% had significant prostate cancer (definitions 1 to 4). For significant cancer sensitivity was 93% to 96%, specificity was 47% to 53%, and negative and positive predictive values were 92% to 96% and 43% to 57%, respectively (definitions 1 to 4). Radical prostatectomy results in 48 men were similar. Aggregate PI-RADS (4 to 20) performed similarly to overall PI-RADS (1 to 5). Negative and positive predictive values (100% and 71%, respectively) were similar in men at higher risk, defined as prostate specific antigen greater than 10 ng/ml with abnormal digital rectal examination. On multivariate analysis PI-RADS score was associated with significant prostate cancer (p <0.001) but magnet strength was not. Adding PI-RADS to the multivariate model improved the AUC from 0.810 to 0.913 (95% CI 0.038-0.166, p = 0.002). Radiologist agreement was substantial (weighted κ = 0.626). Multiparametric magnetic resonance imaging reported by expert radiologists achieved an excellent negative predictive value and a moderate positive predictive value for significant prostate cancer at 1.5 and 3.0 Tesla.

Should experienced open prostatic surgeons convert to robotic surgery? The real learning curve for one surgeon over 3 years

Publisher: Wiley

Date: 13-07-2010

DOI: 10.1111/J.1464-410X.2009.09158.X

Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control.

Publisher: Springer Science and Business Media LLC

Date: 13-10-2015

DOI: 10.1038/PCAN.2015.47

Abstract: Current data on the use of irreversible electroporation (IRE) in the treatment of prostate cancer (PCa) is limited. We aim to evaluate the safety, short-term functional and oncological outcomes of focal IRE in low-intermediate risk PCa. Between February 2013 and May 2014, 32 consecutive men underwent IRE at a single centre. Patients with low-intermediate risk PCa who had not received previous PCa treatment were included for analysis. The tumour was ablated using 3-6 electrodes, ensuring a minimum 5-mm safety margin around the visible magnetic resonance imaging (MRI) lesion. Follow-up included recording Clavien complications, Expanded Prostate Cancer Index Composite (EPIC) questionnaires (baseline, 1.5, 3, 6 months), 6-month multi-parametric MRI (mp-MRI) and 7-month biopsy. Findings on mp-MRI and biopsy were sub- ided into infield, adjacent or outfield of the treatment zone. Twenty-five men were included for final analysis. Safety follow-up revealed one Clavien Grade 3 complication and five Grade 1 complications. Functional follow-up confirmed no significant change in American Urological Association urinary symptom score, sexual or bowel function. Infield, there were no suspicious findings on mp-MRI (n=24) or biopsy (n=21) in all patients. Adjacent to the treatment zone, five (21%) had suspicious findings on mp-MRI with four (19%) proving to be significant on biopsy. Outfield, there were two (8%) with suspicious findings on mp-MRI and one (5%) significant finding on biopsy. For the five patients with significant findings on follow-up biopsy, one is awaiting repeat IRE, one had radical prostatectomy and three remained on active surveillance. In selected patients with low-intermediate risk PCa, focal IRE appears to be safe with minimal morbidity. There were no infield recurrences and 76% of patients were histologically free of significant cancer at 8 months. Almost all recurrences were adjacent to the treatment zone, and this was addressed by widening the treatment margins.

Enduring epigenetic landmarks define the cancer microenvironment

Publisher: Cold Spring Harbor Laboratory

Date: 12-04-2018

DOI: 10.1101/GR.229070.117

Abstract: The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic s les.

Synchronous vs independent reading of prostate‐specific membrane antigen positron emission tomography (PSMA‐PET) and magnetic resonance imaging (MRI) to improve diagnosis of pros

Publisher: Wiley

Date: 05-12-2022

DOI: 10.1111/BJU.15929

Abstract: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68 Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. ‘Concordance’ between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the in idual reporters for each modality. International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.

Enhancing active surveillance of prostate cancer: The potential of exercise medicine

Publisher: Springer Science and Business Media LLC

Date: 08-03-2016

DOI: 10.1038/NRUROL.2016.46

Abstract: Active surveillance (AS) is a strategy for the management of patients with low-risk, localized prostate cancer, in which men undergo regular monitoring of serum PSA levels and tumour characteristics, using multiparametric MRI and repeat biopsy s ling, to identify signs of disease progression. This strategy reduces overtreatment of clinically insignificant disease while also preserving opportunities for curative therapy in patients whose disease progresses. Preliminary studies of lifestyle interventions involving basic exercise advice have indicated that exercise reduces the numbers of patients undergoing active treatment, as well as modulating the biological processes involved in tumour progression. Therefore, preliminary evidence suggests that lifestyle and/or exercise interventions might have therapeutic potential in this growing population of men with prostate cancer. However, several important issues remain unclear: the exact value of different types of lifestyle and exercise medicine interventions during AS the biological mechanisms of exercise in delaying disease progression and the influence of the anxieties and distress created by having a diagnosis of cancer without then receiving active treatment. Future studies are required to confirm and expand these findings and determine the relative contributions of each lifestyle component to specific end points and patient outcomes during AS.

Irreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment

Publisher: Wiley

Date: 05-12-2020

DOI: 10.1111/BJU.14951

Abstract: Whilst whole-gland radical treatment is highly effective for prostate cancer control, it has significant impact on quality of life and is unnecessary 'over-treatment' in many men with screening-detected prostate cancer. Improvements in prostate biopsy and imaging have led to increased interest in partial gland ablation to reduce treatment-related morbidity. Several energies for focal ablation have been trialled. Irreversible electroporation (IRE) is a novel technology that ablates tissue by delivering direct current between electrodes. This narrative review documents the history of electroporation including its scientific basis, early data from pre-clinical animal studies, and contemporary clinical outcomes from the use of IRE in prostate cancer. A literature search using the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), PubMed and Google Scholar was undertaken to identify historical perspectives and current clinical data relating to IRE for prostate cancer. The history of electroporation and its implementation as a prostate cancer treatment was following the basic scientific principles, in vitro data, then animal studies, and now short- to medium-term clinical cohorts in humans. The results of IRE on >283 patients have been published in several papers, with preserved rates of (pad-free) continence in 91-100% of men and preserved erectile function in 79-100% of men. In-field recurrence rates range from 0% to 33%. The current state of evidence for IRE for the treatment of primary and salvage prostate cancer is considered as Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) stage 2B. IRE is a new focal ablative technology for the treatment of localised prostate cancer in carefully selected men. Published cohorts report encouraging short-term oncological and functional outcomes however, longer-term data are needed to validate this treatment before it can be recommended for widespread clinical use.

Focal irreversible electroporation as primary treatment for localized prostate cancer

Publisher: Wiley

Date: 04-09-2017

DOI: 10.1111/BJU.13983

Abstract: To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary focal irreversible electroporation (IRE) for the treatment of localized prostate cancer (PCa), and to identify potential risk factors for oncological failure. Patients who met the consensus guidelines on patient criteria and selection methods for primary focal therapy were eligible for analysis. Focal IRE was performed for organ-confined clinically significant PCa, defined as high-volume disease with Gleason sum score 6 (International Society of Urological Pathology [ISUP] grade 1) or any Gleason sum score of 7 (ISUP grades 2-3). Oncological, adverse event (AE) and QoL outcome data, with a minimum of 6 months' follow-up, were analysed. Patient characteristics and peri-operative treatment variables were compared between patients with and without oncological failure on follow-up biopsy. Wilcoxon's signed rank test, Wilcoxon's rank sum test and the chi-squared test were used to assess statistically significant differences in paired continuous, unpaired continuous and categorical variables respectively. A total of 63 patients met all eligibility criteria and were included in the final analysis. No high-grade AEs occurred. QoL questionnaire analysis demonstrated no significant change from baseline in physical (P = 0.81), mental (P = 0.48), bowel (P = 0.25) or urinary QoL domains (P = 0.41 and P = 0.25), but there was a mild decrease in the sexual QoL domain (median score 66 at baseline vs 54 at 6 months P < 0.001). Compared with baseline, a decline of 70% in prostate-specific antigen level (1.8 ng/mL, interquartile range 0.96-4.8 ng/mL) was seen at 6-12 months. A narrow safety margin (P = 0.047) and system errors (P = 0.010) were identified as potential early risk factors for in-field oncological failure. In-field and whole-gland oncological control on follow-up biopsies was 84% (38/45 patients) and 76% (34/45 patients) this increased to 97% (38/39 patients) and 87% (34/39 patients) when patients treated with a narrow safety margin and system errors were excluded. Our data support the safety and feasibility of focal IRE as a primary treatment for localized PCa with effective short-term oncological control in carefully selected men.

Salvage irreversible electroporation for radio-recurrent prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 03-2023

DOI: 10.1038/S41585-023-00750-1

Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy.

Publisher: Springer Science and Business Media LLC

Date: 28-03-2018

DOI: 10.1007/S00345-018-2281-Z

Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis

Publisher: Springer Science and Business Media LLC

Date: 10-05-2021

DOI: 10.1186/S13073-021-00885-Z

Abstract: High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of s les, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms. Using the Chromium 10X platform, we sequenced a total of ~ 120,000 cells from fresh and cryopreserved replicates across three primary breast cancers, two primary prostate cancers and a cutaneous melanoma. We performed detailed analyses between cells from each condition to assess the effects of cryopreservation on cellular heterogeneity, cell quality, clustering and the identification of gene ontologies. In addition, we performed single-cell immunophenotyping using CITE-Seq on a single breast cancer s le cryopreserved as solid tissue fragments. Tumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on the results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for detecting cell-surface proteins using CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing. We show that the viable cryopreservation of human cancers provides high-quality single-cells for multi-omics analysis. Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies.

The role of magnetic resonance imaging in the diagnosis and management of prostate cancer

Publisher: Wiley

Date: 15-10-2013

DOI: 10.1111/BJU.12381

Abstract: The diagnosis of prostate cancer has long been plagued by the absence of an imaging tool that reliably detects and localises significant tumours. Recent evidence suggests that multi-parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. This review serves as a background to a recent USANZ position statement. It aims to provide an overview of MRI techniques and to critically review the published literature on the clinical application of MRI in prostate cancer. The combination of anatomical (T2-weighted) MRI with at least two of the three functional MRI parameters - which include diffusion-weighted imaging, dynamic contrast-enhanced imaging and spectroscopy - will detect greater than 90% of significant (moderate to high risk) tumours however MRI is less reliable at detecting tumours that are small (<0.5 cc), low grade (Gleason score 6) or in the transitional zone. The higher anatomical resolution provided by 3-Tesla magnets and endorectal coils may improve the accuracy, particularly in primary tumour staging. The use of mpMRI to determine which men with an elevated PSA should undergo biopsy is currently the subject of two large clinical trials in Australia. MRI should be used with caution in this setting and then only in centres with established uro-radiological expertise and quality control mechanisms in place. There is sufficient evidence to justify using MRI to determine the need for repeat biopsy and to guide areas in which to focus repeat biopsy. MRI-directed biopsy is an exciting concept supported by promising early results, but none of the three proposed techniques have so far been proven superior to standard biopsy protocols. Further evidence of superior accuracy and core-efficiency over standard biopsy is required, before their costs and complexities in use can be justified. When used for primary-tumour staging (T-staging), MRI has limited sensitivity for T3 disease, but its specificity of greater than 95% may be useful in men with intermediate-high risk disease to identify those with advanced T3 disease not suitable for nerve sparing or for surgery at all. MRI appears to be of value in planning dosimetry in men undergoing radiotherapy, and in guiding selection for and monitoring on active surveillance.

Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer.

Publisher: Wiley

Date: 19-09-2017

DOI: 10.1111/BJU.13991

Abstract: To evaluate the feasibility, safety, early quality-of-life (QoL) and oncological outcomes of salvage focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa). Patients with localized, radio-recurrent PCa without evidence of metastatic or nodal disease were offered focal IRE according to the consensus guidelines. Patients with a minimum follow-up of 6 months were eligible for analysis. Adverse events were monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Patient-reported QoL data were collected at baseline, 6 weeks, 3, 6 and 12 months using the Expanded Prostate Cancer Index Composite (EPIC), the American Urological Association (AUA) symptom score and the 12-item short-from health survey (SF-12) physical and mental component summary questionnaires. Oncological control was evaluated according to serial prostate-specific antigen (PSA), 6-month multiparametric magnetic resonance imaging (mpMRI) and 12-month prostate biopsy. Wilcoxon's signed rank test was used to assess QoL differences over time in paired continuous variables. A total of 18 patients were included in the analysis. The median follow-up was 21 months. No high-grade adverse events (CTCAE >2) or recto-urethral fistulae occurred. No statistically significant declines were observed in QoL outcomes (n = 11) on the EPIC bowel domain (P = 0.29), AUA symptom score (P = 0.77), or the SF-12 physical (P = 0.17) or SF-12 mental component summary (P = 0.77) questionnaires. At 6 months, patients who had undergone salvage therapy experienced a decline in EPIC sexual domain score (median of 38-24 P = 0.028) and urinary domain (median of 96-92 P = 0.074). Pad-free continence and erections sufficient for intercourse were preserved in 8/11 patients and 2/6 patients at 6 months, respectively. The mpMRI was clear in 11/13 patients, with two single out-field lesions (true-positive and false-positive, respectively). The median (interquartile range) nadir PSA was 0.39 (0.04-0.43) μg/L. Three and four patients experienced biochemical failure using the Phoenix and Stuttgart definitions of biochemical failure, respectively. Eight out of 10 of the patients were clear of any PCa on follow-up biopsy, whereas two patients had significant PCa on follow-up biopsy (International Society of Urological Pathology grade 5). Our short-term safety, QoL and oncological control data show that focal IRE is a feasible salvage option for localized radio-recurrent PCa. A prospective multicentre study (FIRE trial) has been initiated that will provide further insight into the ability of focal IRE to obtain oncological control of radio-recurrent PCa with acceptable patient morbidity.

Aberrant neuropeptide Y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis

Publisher: American Association for Cancer Research (AACR)

Date: 04-2006

DOI: 10.1158/1055-9965.EPI-05-0752

Abstract: Studies to elucidate dysregulated gene expression patterns in premalignant prostate lesions have identified several candidate genes with the potential to be targeted to prevent the development and progression of prostate cancer and act as biomarkers of early disease. Herein, we explored the importance of two proteins, neuropeptide Y (NPY) and macrophage inhibitory cytokine-1 (MIC-1), as biomarkers of preinvasive prostate disease and investigated the relationship of expression to biochemical recurrence following treatment for localized prostate cancer. NPY and MIC-1 protein expression was determined by immunohistochemistry on tissue microarrays containing 1,626 cores of benign, low-grade prostatic intraepithelial neoplasia (PIN), high-grade PIN (HGPIN), and prostate cancer tissue from 243 radical prostatectomy patients. Both NPY and MIC-1 showed higher proportional immunostaining in HGPIN and prostate cancer compared with benign epithelium (P & 0.0001). NPY and MIC-1 immunostaining was higher in low-grade PIN compared with other benign tissues (both P & 0.0001) and was equivalent to immunostaining in HGPIN. NPY immunostaining of prostate cancer was independently associated with relapse, after adjusting for traditional prognostic factors, as a categorical variable in 20% intervals (P = 0.0449-0.0103) and as a continuous variable (P = 0.0017). Low MIC-1 immunostaining (20% categories) was associated with pathologic stage & C after adjusting for predictors of pathologic stage (P = 0.3894-0.0176). This is the first study to show that altered NPY and MIC-1 expression are significantly associated with prostate cancer progression and suggests that these molecules be developed further as biomarkers in the management of prostate disease. (Cancer Epidemiol Biomarkers Prev 2006 (4):711–6)

Revisiting Delphi to Create a Basis for the Future of Focal Therapy for Prostate Cancer

Publisher: XMLink

Date: 2023

DOI: 10.5534/WJMH.230160

Reduced sensitivity of multiparametric MRI for clinically significant prostate cancer in men under the age of 50

Publisher: Informa UK Limited

Date: 10-2018

DOI: 10.2147/RRU.S169017

African-specific molecular taxonomy of prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 31-08-2022

DOI: 10.1038/S41586-022-05154-6

Abstract: Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages 1 . The contributing genetic and non-genetic factors, and associated mutational processes, are unknown 2,3 . Here, through whole-genome sequencing of treatment-naive prostate cancer s les from 183 ancestrally (African versus European) and globally distinct patients, we generate a large cancer genomics resource for sub-Saharan Africa, identifying around 2 million somatic variants. Significant African-ancestry-specific findings include an elevated tumour mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations and a higher total of mutational signatures, and the driver genes NCOA2 , STK19 , DDX11L1 , PCAT1 and SETBP1 . Examining all somatic mutational types, we describe a molecular taxonomy for prostate cancer differentiated by ancestry and defined as global mutational subtypes (GMS). By further including Chinese Asian data, we confirm that GMS-B (copy-number gain) and GMS-D (mutationally noisy) are specific to African populations, GMS-A (mutationally quiet) is universal (all ethnicities) and the African–European-restricted subtype GMS-C (copy-number losses) predicts poor clinical outcomes. In addition to the clinical benefit of including in iduals of African ancestry, our GMS subtypes reveal different evolutionary trajectories and mutational processes suggesting that both common genetic and environmental factors contribute to the disparity between ethnicities. Analogous to gene–environment interaction—defined here as a different effect of an environmental surrounding in people with different ancestries or vice versa—we anticipate that GMS subtypes act as a proxy for intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.

A novel method of bladder neck imbrication to improve early urinary continence following robotic-assisted radical prostatectomy

Publisher: Springer Science and Business Media LLC

Date: 26-07-2012

DOI: 10.1007/S11701-012-0371-2

Abstract: Early return of continence forms an important component of quality of life for patients after robotic-assisted radical prostatectomy (RALP). Here we describe the steps of bladder neck imbrication and vesico-urethral anastomosis improving early continence after RALP. Between April 2008 and July 2009, 202 consecutive patients underwent RALP for clinically localised prostate cancer in a tertiary referral centre by a single surgeon. One hundred and thirty-two (65 %) of these patients agreed to participate in the study. Prior to November 2008, 51 patients underwent standard RALP as described by Patel et al. From November 2008, 81 patients underwent a novel method of bladder neck imbrication. The robotic urethro-vesical anastomosis commences on the posterior wall of the urethra and proceeds anteriorly. In our technique the anastomosis is halted with the suture arms fixed to the anterior abdominal wall. A new suture is used to perform a two-layer repair, anchoring proximally then continuing anteriorly to the level of the urethral stump, where it returns upon itself. The aim is to narrow the urethra to 16 Fr and tighten the second layer to create an imbrication effect. Posterior reconstruction was performed in all patients. Outcome measures were recorded prospectively using the Expanded Prostate Cancer Index Composite tool. Our technique shows significant improvement at all stages of follow-up in urinary summary and incontinence scores. Absolute continence rates increased from 8.2 to 20.5 %, 26.7 to 44.3 %, and 47.7 to 62.3 % at 1.5, 3 and 6 months, respectively. These results support the use of our technique in patients undergoing RALP.

An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy.

Publisher: Wiley

Date: 04-12-2018

DOI: 10.1002/IJC.31906

Initial multicentre experience of (68)gallium-PSMA PET/CT guided robot-assisted salvage lymphadenectomy: acceptable safety profile but oncological benefit appears limited

Publisher: Wiley

Date: 20-06-2017

DOI: 10.1111/BJU.13919

Abstract: To evaluate the safety and short-term oncological outcomes of Between February 2014 and April 2016, 35 patients across two centres underwent RASND for A total of 58 lesions suspicious for lymph node metastases (LNM) in 35 patients were detected on Although RASND appears safe and feasible, less than half of our cohort had a treatment response, and less than a quarter experienced BCR-free survival at 12-month median follow-up.

High‐dose rate brachytherapy compared with open radical prostatectomy for the treatment of high‐risk prostate cancer: 10 year biochemical freedom from relapse

Publisher: Wiley

Date: 29-11-2012

DOI: 10.1111/J.1464-410X.2012.11480.X

A multi-center international study to evaluate the safety, functional and oncological outcomes of Irreversible Electroporation for the ablation of prostate cancer

Publisher: Research Square Platform LLC

Date: 08-09-2023

DOI: 10.21203/RS.3.RS-3248717/V1

A prospective multicentre phase III validation study of AZGP1 as a biomarker in localized prostate cancer

Publisher: Elsevier BV

Date: 08-2017

DOI: 10.1093/ANNONC/MDX247

Abstract: Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying in iduals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC. In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS). In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4 95% CI, 1.1-1.9 P = 0.03), MFS (HR, 2.8 95% CI, 1.2-6.6 P = 0.02) and PCSS (HR, 3.8 95% CI, 1.5-9.5 P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9 95% CI, 1.1-3.3 P = 0.02), with shorter MFS (HR, 2.0 95% CI, 1.1-3.4 P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models. Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.

Guidelines for whole genome bisulphite sequencing of intact and FFPET DNA on the Illumina HiSeq X Ten

Publisher: Springer Science and Business Media LLC

Date: 28-05-2018

DOI: 10.1186/S13072-018-0194-0

Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies.

Publisher: Hindawi Limited

Date: 2016

DOI: 10.1155/2016/7105678

Abstract: Introduction . To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC). Materials and Methods . Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA ng/mL, Gleason score PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1–5, criterion 1 stringent (Gleason score 6 + ≤5 mm total max core length PC + ≤3 mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume .5 mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume .7 mL). Results . 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC. Conclusions . Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies.

Robot-assisted laparoscopic prostatectomy: analysis of an experienced open surgeon’s learning curve after 300 procedures

Publisher: Springer Science and Business Media LLC

Date: 2010

DOI: 10.1007/S11701-010-0171-5

Abstract: To critically analyse the learning curve for a single experienced open surgeon converting to robotic surgery. From February 2006 to July 2009, 300 patients underwent a robot-assisted laparoscopic prostatectomy (RALP) by a single urologist. This study is a prospective analysis of the baseline patient and tumour characteristics, intraoperative and postoperative data, and histopathologic features. To analyse the RALP learning curve, the joinpoint regression method was used. Mean age of the patient was 61.3 years (range 46-76). Mean pre-operative PSA level was 7 ng/ml (range 0.7-41), and follow-up was 14 months (0.7-41). The mean operating time was 185 min (range 119-525). One hundred and ten cases were required to achieve 3-h proficiency. There were no conversions. The mean hospital stay was 2.8 days (range 2-7). Major complications rate was 1.3%. The blood transfusion rate was 0.6%. The overall positive surgical margin (PSM) rate was 21.3%. pT2 and pT3 PSM rate was 10 and 44%, respectively. The joinpoint regression method showed that the learning curve started to plateau for the overall PSM rate after 205 cases (95% CI 200-249). For pT2 and pT3, PSM rate, the learning curve tended to flatten after 130 and 170 cases, respectively. The analysis of an experienced open surgeon learning curve in transferring his skills to the robotic platform has shown that 3-h proficiency requires 110 cases. The overall, pT2, and pT3 PSM rate take approximately 200, 130, and 170 cases, respectively, to flatten.

Low AZGP1 expression predicts for recurrence in margin-positive, localized prostate cancer

Publisher: Wiley

Date: 22-03-2011

DOI: 10.1002/PROS.21381

Abstract: Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40-50% biochemical relapse rate at 5 years. Adjuvant radiotherapy improves biochemical progression-free and overall survival in men with positive margins, but is associated with increased toxicity. There is an urgent need to identify new prognostic markers to define the group of patients who would benefit from multimodality therapy. Nuclear β-catenin, membranous secreted frizzled-related protein 4 (sFRP4), zinc-alpha 2-glycoprotein (AZGP1), and macrophage inhibitory cytokine-1 (MIC-1) have previously been identified as molecular markers of outcome in localized PC. From these published studies, we identified a subset of patients with positive margins. The aim of this study was to assess the association between these four molecular markers and outcome in men with margin-positive, localized PC. We identified 186 men with positive margins from 330 men with localized PC 53% had preoperative PSA >10 ng/ml, 72% extraprostatic extension (EPE), 24% seminal vesicles involvement (SVI), and 57% RP Gleason score ≥ 7. AZGP1 (P = 0.009), membranous sFRP4 (P = 0.03) and MIC-1 (P = 0.04) expression predicted for biochemical relapse on univariate analysis. Only absent/low AZGP1 expression (P = 0.01) was an independent predictor of recurrence in margin-positive, localized PC when modeled with preoperative PSA (P = 0.2), EPE (P = 0.2), SVI (P = 0.4), Gleason score ≥ 7 (P = 0.5) and adjuvant treatment (P = 0.4). Furthermore, there was an association between absent/low AZGP1 expression and clinical recurrence (P = 0.007). AZGP1 is a potential molecular marker for biochemical relapse in men with margin-positive, localized PC. Routine assessment of this biomarker may lead to better selection of patients who will benefit from post-RP radiotherapy.

Évaluation de la qualité de vie suite aux traitements actuels du cancer de prostate localisé

Publisher: Elsevier BV

Date: 11-2013

DOI: 10.1016/J.PUROL.2013.08.187

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer

Publisher: Wiley

Date: 14-11-2018

DOI: 10.1002/PROS.23440

Abstract: Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis.

The Magnetic Resonance Imaging in Active Surveillance (MRIAS) Trial: Use of Baseline Multiparametric Magnetic Resonance Imaging and Saturation Biopsy to Reduce the Frequency of Surveillance Prostate B

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2020

DOI: 10.1097/JU.0000000000000693

Whole-Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating Driver Mutations in African Men with Treatment-Naïve, High-Risk Prostate Cancer.

Publisher: American Association for Cancer Research (AACR)

Date: 13-12-2018

DOI: 10.1158/0008-5472.CAN-18-0254

Abstract: The first whole-genome sequencing study for high-risk prostate cancer in African men allows a simultaneous comparison of ethnic differences relative to European populations and of the influences of the environment relative to African-American men.

Median 4‐year outcomes of salvage irreversible electroporation for localized radio‐recurrent prostate cancer

Publisher: Wiley

Date: 03-01-2023

DOI: 10.1111/BJU.15948

Abstract: To evaluate the safety, and short to mid‐term oncological and quality‐of‐life (QoL) outcomes of focal irreversible electroporation (IRE) for radio‐recurrent prostate cancer (PCa) at a median follow‐up of 4 years. This was a single‐centre series of men with biopsy‐proven radio‐recurrent PCa treated with IRE between December 2013 and February 2022, with a minimum follow‐up of 6 months. Follow‐up included magnetic resonance imaging at 6 months, and standard transperineal saturation template biopsies at 12 months. Further biopsies were guided by suspicion on serial imaging or prostate‐specific antigen (PSA) levels. Validated questionnaires were used to measure functional outcomes. Significant local recurrence was defined as any International Society of Urological Pathology (ISUP) score ≥ 2 on biopsies. Progression‐free survival was defined as no signs of local or systemic disease on either imaging or template biopsies, or according to the Phoenix criteria for biochemical recurrence. Final analysis was performed on 74 men with radio‐recurrent PCa (median age 69 years, median PSA level 5.4 ng/mL, 76% ISUP score 2/3). The median (range) follow‐up was 48 (27–68) months. One rectal fistula occurred, and eight patients developed urethral sloughing that resolved with transurethral resection. Among patients who returned questionnaires (30/74, 41%), 93% (28/30) had preserved urinary continence and 23% (7/30) had sustained erectile function at 12‐month follow‐up. Local control was achieved in 57 patients (77%), who needed no further treatment. Biopsy diagnosed 41(55%) patients received follow up template biopsies, in‐field recurrences occurred in 7% (3/41), and out‐field recurrences occurred in 15% of patients (6/41). The metastasis‐free survival rate was 91% (67/74), with a median (interquartile range) time to metastases of 8 (5–27) months. The Kaplan–Meier estimated 5‐year progression‐free survival rate was 60%. These short‐ to mid‐term safety, oncological and QoL outcome data endorse results from smaller series and show the ability of salvage focal IRE to safely achieve oncological control in patients with radio‐recurrent PCa.

Quality of life three years after diagnosis of localised prostate cancer: population based cohort study

Publisher: BMJ

Date: 27-11-2009

DOI: 10.1136/BMJ.B4817

Gene based prediction of clinically localized prostate cancer progression after radical prostatectomy.

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 10-2010

DOI: 10.1016/J.JURO.2010.05.084

Abstract: Accurate estimates of recurrence risk are needed for optimal treatment of patients with clinically localized prostate cancer. We combined an established nomogram and what to our knowledge are novel molecular predictors into a new prognostic model of prostate specific antigen recurrence. We analyzed gene expression profiles from formalin fixed, paraffin embedded, localized prostate cancer tissues to identify genes associated with prostate specific antigen recurrence. Profiles of the identified markers were reproduced by reverse transcriptase-polymerase chain reaction. We used the profiles of 3 of these genes along with output from the Kattan postoperative nomogram to produce a predictive model of prostate specific antigen recurrence. After variable selection we built a model of prostate specific antigen recurrence combining expression values of 3 genes and the postoperative nomogram. The 3-gene plus nomogram model predicted 5-year prostate specific antigen recurrence with a concordance index of 0.77 in a validation set compared to a concordance index of 0.67 for the nomogram. This model identified a subgroup of patients at high risk for recurrence that was not identified by the nomogram. This new gene based classifier has superior predictive power compared to that of the 5-year nomogram to assess the risk of prostate specific antigen recurrence in patients with organ confined prostate cancer. Our classifier should provide more accurate stratification of patients into high and low risk groups for treatment decisions and adjuvant clinical trials.

Median 5‐year outcomes of primary focal irreversible electroporation for localised prostate cancer

Publisher: Wiley

Date: 28-12-2022

DOI: 10.1111/BJU.15946

Abstract: To evaluate longer‐term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow‐up of 5 years (up to 10 years). All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow‐up were analysed. Follow‐up included 6‐month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate‐specific antigen (PSA) levels. Failure‐free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy. A total of 229 patients were analysed with a median (interquartile range [IQR]) follow‐up of 60 (40–80) months. The median (IQR) age was 68 (64–74) years, the median (IQR) PSA level was 5.9 (4.1–8.2) ng/mL, and 86% harboured intermediate‐risk disease and 7% high‐risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17–53) months after IRE. Kaplan–Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis‐free survival was 99.6% (228/229), PCa‐specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow‐up biopsy and MRI showed a complete ablation in 82% (186/226). Short‐term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%). Longer‐term follow‐up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long‐term follow‐up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.

Salvage irreversible electroporation for radio‐recurrent prostate cancer – the prospective FIRE trial

Publisher: Wiley

Date: 09-01-2023

DOI: 10.1111/BJU.15947

Abstract: To prospectively assess the safety, functional‐ and oncological‐outcomes of irreversible electroporation (IRE) as salvage therapy for radio‐recurrent focal prostate cancer in a multicenter setting. Men with focal recurrent PCa after external beam radiation or brachytherapy without metastatic disease on staging imaging and co‐registration between mpMRI and biopsies were prospectively included in this multicenter trial. Adverse events were reported following the Clavien‐Dindo classification. Validated questionnaires were used for patient‐reported functional outcomes. Follow‐up consisted of 3 monthly prostate specific antigen (PSA) levels, a 6‐month mpMRI and standardised transperineal template mapping biopsies at 12‐months. Thereafter follow‐up was guided by MRI and/or PSMA‐PET/CT and PSA. Local recurrence was defined as any ISUP score ≥2 on biopsies. 37 patients were analysed with a median (interquartile range (IQR)) follow up of 29 (22–43) months. Median age was 71 (53–83), median PSA was 3.5 ng/mL (2.7–6.1). 28 (75.5%) patients harboured intermediate risk and 9 patients (24.5%) high risk PCa. Seven patients (19%) reported self‐limiting urgency, frequency, or hematuria (grade 1–2). Seven patients (19%) developed a grade 3 AE urethral sludge requiring transurethral resection. At 12 months post treatment 93% of patients remained continent and erectile function sufficient for intercourse deteriorated from 35% to 15% (4/27). Local control was achieved in 29 patients (78%) and 27 patients (73%) were clear of local and systemic disease. Four (11%) patients had local recurrence only. Six (16%) patients developed metastatic disease with a median time to metastasis of 8 months. The FIRE trial shows that salvage IRE after failed radiation therapy for localised PCa is safe with minimal toxicity, and promising functional and oncological outcomes. Salvage IRE can offer a possible solution for notoriously difficult to manage radio recurrent prostate tumours.

Computational imaging reveals shape differences between normal and malignant prostates on MRI

Publisher: Springer Science and Business Media LLC

Date: 02-2017

DOI: 10.1038/SREP41261

Abstract: We seek to characterize differences in the shape of the prostate and the central gland (combined central and transitional zones) between men with biopsy confirmed prostate cancer and men who were identified as not having prostate cancer either on account of a negative biopsy or had pelvic imaging done for a non-prostate malignancy. T2w MRI from 70 men were acquired at three institutions. The cancer positive group (PCa+) comprised 35 biopsy positive (Bx+) subjects from three institutions (Gleason scores: 6–9, Stage: T1–T3). The negative group (PCa−) combined 24 biopsy negative (Bx−) from two institutions and 11 subjects diagnosed with rectal cancer but with no clinical or MRI indications of prostate cancer (Cl−). The boundaries of the prostate and central gland were delineated on T2w MRI by two expert raters and were used to construct statistical shape atlases for the PCa+, Bx− and Cl− prostates. An atlas comparison was performed via per-voxel statistical tests to localize shape differences (significance assessed at p 0.05). The atlas comparison revealed central gland hypertrophy in the Bx− subpopulation, resulting in significant volume and posterior side shape differences relative to PCa+ group. Significant differences in the corresponding prostate shapes were noted at the apex when comparing the Cl− and PCa+ prostates.

Prostate cancer in 432 men aged <50 years in the prostate-specific antigen era: a new outlook.

Publisher: Wiley

Date: 11-2018

DOI: 10.1111/BJU.14586

Abstract: To evaluate the clinical presentation and treatment outcomes of prostate cancer (PCa) in 432 consecutive patients aged < 50 years in the prostate-specific antigen (PSA) era. Retrospective analysis was performed on all patients with PCa (14 570) from the years 1994 to 2017. A total of 432 consecutive patients aged < 50 years were identified. The patients were stratified by D'Amico risk groups, and their clinical presentation and treatment outcomes were analysed. The rates of biochemical recurrence after surgery were compared with the D'Amico prediction model as well as with older propensity-score-matched patients. The surgical pathology results in patients undergoing active surveillance (AS) were compared with those of low-risk patients who underwent immediate surgery. A total of 44%, 42% and 13% of patients harboured low-risk, intermediate-risk and high-risk PCa, respectively. Their median age was 47 years and a positive family history of PCa was reported in 39.1%. Clinical stage was T1 in 65.5% and T2 in 30.0% of patients, and 2.0% of patients had metastatic disease at presentation. Radical prostatectomy (RP) was performed in 78.4% of patients (n = 339) and the biochemical recurrence rates were 7.8% (low-risk), 15.3% (intermediate-risk) and 23.3% (high-risk) at 5 years post-surgery. These rates were lower than expected according to the D'Amico prediction model or when compared with older matched patients. A total of 74 patients with low-risk PCa underwent AS and only 17.6% (n = 13) required radical treatment after a median follow-up of 46 months. The surgical pathology results in patients undergoing ASdid not differ significantly from patients with low-risk PCa who underwent immediate surgery (positive surgical margins [P = 0.145], tumour volume [P = 0.257] or seminal vesicle involvement [P = 0.100]). Of the present cohort, only 0.4% died from PCa during a median follow-up of 65 months. The clinical presentation and prognosis of young patients has changed dramatically during the PSA era. Patients nowadays present with lower-risk disease that can be treated adequately, with reassuring biochemical recurrence rates at 5 years post-surgery. AS appears to be safe in patients with low-risk. PCa.

Assessment of the Performance of Magnetic Resonance Imaging/Ultrasound Fusion Guided Prostate Biopsy against a Combined Targeted Plus Systematic Biopsy Approach Using 24-Core Transperineal Template Saturation Mapping Prostate Biopsy.

Publisher: Hindawi Limited

Date: 2016

DOI: 10.1155/2016/3794738

Abstract: Objective. To compare the performance of multiparametric resonance imaging/ultrasound fusion targeted biopsy (MRI/US-TBx) to a combined biopsy strategy (MRI/US-TBx plus 24-core transperineal template saturation mapping biopsy (TTMB)). Methods. Between May 2012 and October 2015, all patients undergoing MRI/US-TBx at our institution were included for analysis. Patients underwent MRI/US-TBx of suspicious lesions detected on multiparametric MRI + / - simultaneous TTMB. Subgroup analysis was performed on patients undergoing simultaneous MRI/US-TBx + TTMB. Primary outcome was PCa detection. Significant PCa was defined as ≥Gleason score (GS) 3 + 4 = 7 PCa. McNemar’s test was used to compare detection rates between MRI/US-TBx and the combined biopsy strategy. Results. 148 patients underwent MRI/US-TBx and 80 patients underwent MRI/US-TBx + TTMB. In the MRI/US-TBx versus combined biopsy strategy subgroup analysis ( n = 80 ), there were 55 PCa and 38 significant PCa. The detection rate for the combined biopsy strategy versus MRI/US-TBx for significant PCa was 49% versus 40% ( p = 0.02 ) and for insignificant PCa was 20% versus 10% ( p = 0.04 ), respectively. Eleven cases (14%) of significant PCa were detected exclusively on MRI/US-TBx and 7 cases (8.7%) of significant PCa were detected exclusively on TTMB. Conclusions. A combined biopsy approach (MRI/US-TBx + TTMB) detects more significant PCa than MRI/US-TBx alone however, it will double the detection rate of insignificant PCa.

ABSTRACTS

Publisher: Wiley

Date: 06-02-2009

DOI: 10.1111/J.1464-410X.2009.09021.X

Accuracy of Primary Systematic Template Guided Transperineal Biopsy of the Prostate for Locating Prostate Cancer: A Comparison With Radical Prostatectomy Specimens

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 06-2012

DOI: 10.1016/J.JURO.2012.01.066

Abstract: We determined whether systematic template guided transperineal biopsies can accurately locate and sensitively detect prostate cancer. In addition, we reported discrepancies between diagnostic and pathological Gleason scores, and investigated whether prostate size had an effect on the cancer detection rate. This retrospective diagnostic accuracy study compares the results of primary transperineal biopsies with the radical prostatectomy pathology of 414 consecutive patients treated at a single institution between November 2002 and August 2010. The average sensitivity and specificity for the detection of cancer in all prostates across all biopsy zones was 48% (95% CI 42.6-53.4) and 84.1% (95% CI 80-88.2), respectively. There was a statistically significant decrease in the sensitivity of transperineal biopsy in larger prostates (t11=4.687, p=0.001). The overall Kappa value was 0.255 (95% CI 0.212-0.298). Grading concordance between biopsy and pathology specimens was achieved in 65.7% of patients. Upgrading of Gleason scores occurred in 25.6% of patients and downgrading occurred in 8.8%. Our current transperineal biopsy method has only demonstrated fair agreement with the histopathology findings of the corresponding radical prostatectomy specimens. This finding is most likely due to the small, multifocal nature of prostate cancer in the patient series. The cancer detection rate was lower in larger prostates. Thus, clinicians may consider increasing the number of cores in larger prostates as a strategy to improve cancer detection.

Combination of multiparametric MRI and transperineal template-guided mapping biopsy of the prostate to identify candidates for hemi-ablative focal therapy

Publisher: Wiley

Date: 11-05-2015

DOI: 10.1111/BJU.13090

Abstract: To evaluate the accuracy of combined multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) for identifying lobes with significant prostate cancer (PCa) for the application of hemi-ablative focal therapy (FT). From January 2012 to January 2014, 89 consecutive patients, aged ≥40 years, with a PSA level ≤15 ng/mL, underwent in sequential order: mpMRI, TTMB and radical prostatectomy (RP) at a single centre. Analysis was performed on 50 patients who met consensus guidelines for FT. Lobes were stratified into lobes with significant cancer (LSC), lobes with insignificant cancer and lobes with no cancer. Using histopathology at RP, the predictive performance of combined mpMRI + TTMB in identifying LSC was evaluated. The sensitivity, specificity and positive predictive value for mpMRI + TTMB for LSC were 97, 61 and 83%, respectively. The negative predictive value (NPV), the primary variable of interest, for mpMRI + TTMB for LSC was 91%. Of the 50 patients, 21 had significant unilateral disease on mpMRI + TTMB. Two of these 21 patients had significant bilateral disease on RP not identified on mpMRI + TTMB. In the selection of candidates for FT, a combination of mpMRI and TTMB provides a high NPV in the detection of LSC.

Reply to Patrick H. Tuliao and Koon Ho Rha's letter to the editor re: James E. Thompson, Sam Egger, Maret Böhm, et al. Superior quality of life and improved surgical margins are achievable with robotic radical prostatectomy after a long learning curve: a prospective single-surgeon study of 1552 consecutive cases. Eur Urol 2014;65:521-31.

Publisher: Elsevier BV

Date: 06-2014

DOI: 10.1016/J.EURURO.2014.01.021

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

Publisher: Wiley

Date: 31-03-2017

DOI: 10.1111/BJU.13814

Abstract: To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap res ling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer. In idualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed.

Outcomes of transperineal template‐guided prostate biopsy in 409 patients

Publisher: Wiley

Date: 03-04-2013

DOI: 10.1111/J.1464-410X.2012.11657.X

Gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer

Publisher: Wiley

Date: 07-04-2019

DOI: 10.1111/BJU.14506

Abstract: To determine the value of gallium-68-prostate-specific membrane antigen ( We analysed results of 140 men with intermediate- and high-risk prostate cancer. All men underwent In these 140 patients with intermediate- and high-risk prostate cancer, 27.1% had PSMA PET/CT-positive findings in the pelvic LNs. Sensitivity and specificity for detection of LN metastases were 53% and 88% (PSMA PET/CT) and 14% and 99% (mpMRI), respectively. The overall BCP rate was 25.7%. The BCP rate was 16.7% in men who were PSMA PET/CT LN-negative compared to 50% in men who were PSMA PET/CT LN-positive (P < 0.05). The presence of PSMA-positive pelvic LNs was more predictive of BCP after RP than cT-stage, PSA level, and the Gleason score, adjusted for surgical margins status.

Overcoming enzalutamide resistance in metastatic prostate cancer by targeting sphingosine kinase

Publisher: Elsevier BV

Date: 10-2021

DOI: 10.1016/J.EBIOM.2021.103625

Radiomic features on MRI enable risk categorization of prostate cancer patients on active surveillance: Preliminary findings

Publisher: Wiley

Date: 22-02-2018

DOI: 10.1002/JMRI.25983

Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy

Publisher: Springer Science and Business Media LLC

Date: 24-07-2008

DOI: 10.1038/IJIR.2008.33

Abstract: Four weeks after bilateral nerve-sparing radical retropubic prostatectomy, men with normal erectile function before surgery were randomized to double-blind sildenafil (50 or 100 mg) or placebo nightly for 36 weeks, followed by an 8-week drug-free period before assessment of erectile function. Enrollment was prematurely ceased and only 76 men completed because, assuming a placebo response rate similar to the published literature (for ex le, 34% in meta-analysis), the 25% response at blinded interim review suggested a lack of treatment effect. On the contrary, spontaneous erectile function (a combined score of >or=8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to 'Were erections good enough for satisfactory sexual activity?') occurred in only 4% of the placebo group (n=1 of 25) versus 27% (n=14 of 51, P=0.0156, Fisher's exact test) of the sildenafil group. Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections.

Preliminary Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Detect Residual Prostate Cancer Following Focal Therapy with Irreversible Electroporation

Publisher: Elsevier BV

Date: 07-2019

DOI: 10.1016/J.EUF.2017.10.007

Abstract: It is recommended to perform multiparametric magnetic resonance imaging (mpMRI) in the follow-up following focal therapy of prostate cancer (PCa). To determine the diagnostic accuracy of mpMRI to detect residual PCa following focal therapy with irreversible electroporation. Seventy-six patients with biopsy-proven localized PCa consented for primary irreversible electroporation between February 2013 and March 2016. Final analysis was performed on 50 patients that received follow-up mpMRI at 6 mo, serial prostate-specific antigen (PSA) testing, and transperineal template-mapping biopsies at 12 mo. Outfield regions of interest (ROI) were reported using PI-RADS version 2. A binary outcome (suspicious vs nonsuspicious) was given for the infield ablation zone. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated for different definitions of significant PCa: (1) Gleason ≥4+3 or Gleason ≥3+3 with a maximum cancer core length ≥6mm, (2) Gleason ≥3+4 or Gleason ≥3+3 with a maximum cancer core length ≥4mm, for outfield and infield ROI. Multivariate linear regression analyses evaluated the additional value of nadir PSA. Sensitivity, specificity, positive predictive values, and negative predictive values of infield ROI was 43%, 86%, 33%, and 90% for definition 1 and 38%, 86%, 33%, and 88% for definition 2, respectively. For outfield ROI this was 33%, 82%, 20%, and 90% for definition 1 and 38%, 86%, 50%, and 80% for definition 2. PSA had no additional value in predicting residual significant PCa. Limitations include retrospective design, single reader, and low incidence of residual PCa. Our preliminary data suggest that mpMRI can rule out high-volume residual PCa. However, follow-up biopsies should still be performed to determine oncological control. Multiparametric magnetic resonance imaging is able to detect high-volume significant prostate cancer following focal therapy. Prostate biopsies are still required in the follow-up of focal therapy as (low-volume) significant prostate cancer is being missed by multiparametric magnetic resonance imaging.

Adverse effects of androgen‐deprivation therapy in prostate cancer and their management

Publisher: Wiley

Date: 04-2015

DOI: 10.1111/BJU.12964

Abstract: To provide an up-to-date summary of current literature on the management of adverse effects of androgen-deprivation therapy (ADT). All relevant medical literature on men with prostate cancer treated with ADT from 2005 to 2014, and older relevant papers, were reviewed. Recent health advisory statements from the Australian government, societies and advocacy groups have been incorporated to the document. There are numerous adverse effects of ADT that require pro-active prevention and treatment. Ranging from cardiovascular disease, diabetes and osteoporosis, to depression, cognitive decline and sexual dysfunction, the range of adverse effects is wide. Baseline assessment, monitoring, prevention and consultation from a multidisciplinary team are important in minimising the harm from ADT. This review provides a series of practical recommendations to assist with managing the adverse effects of ADT.

Naval Medical Center San Diego

Location: United States of America

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Western Sydney University

Location: Australia

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The Kinghorn Cancer Centre

Location: Australia

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St Vincent's Hospital Sydney

Location: Australia

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University Of Western Sydney

Location: No location found

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University Of Tasmania

Location: Australia

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University Of Sydney

Location: Australia

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University Of New South Wales

Location: Australia

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St Vincent's Private Hospital Sydney

Location: Australia

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Australian Prostate Cancer Research Centre

Location: Australia

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