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Purpose: We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa).Methods: Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon's signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume.Results: There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction.Conclusion: IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction. [ABSTRACT FROM AUTHOR]

Diagnostic accuracy of needle-based optical coherence tomography (OCT) for prostate cancer detection by visual and quantitative analysis is defined. 106 three-dimensional (3-D)-OCT data sets were acquired in 20 prostates after radical prostatectomy and precisely matched with pathology. OCT images were grouped per histological category. Two reviewers performed blind assessments of the OCT images. Sensitivity and specificity for malignancy detection were calculated. Quantitative analyses by automated optical attenuation coefficient calculation were performed. OCT can reliably differentiate between fat, cystic, and regular atrophy and benign glands. The overall sensitivity and specificity for malignancy detection was 79% and 88% for reviewer 1 and 88% and 81% for reviewer 2. Quantitative analysis for differentiation between stroma and malignancy showed a significant difference (4.6 mm-1 versus 5.0 mm-1 Mann-Whitney U-test p < 0.0001). A Kruskal-Wallis test showed a significant difference in median attenuation coefficient between stroma, inflammation, Gleason 3, and Gleason 4 (4.6, 4.1, 5.9, and 5.0 mm-1, respectively). However, attenuation coefficient varied per patient and a related-samples Wilcoxon signed-rank test showed no significant difference per patient (p = 0.17). This study confirmed the one to one correlation of histopathology and OCT. Precise matching showed that most histological tissues categories in the prostate could be distinguished by their unique pattern in OCT images. In addition, the optical attenuation coefficient can play a role in the differentiation between stroma and malignancy; however, a per patient analysis of the optical attenuation coefficient did not show a significant difference. [ABSTRACT FROM AUTHOR]

Objective: The role of angiogenesis in cancer growth has stimulated research aimed at noninvasive cancer detection by blood perfusion imaging. Recently, contrast ultrasound dispersion imaging was proposed as an alternative method for angiogenesis imaging. After the intravenous injection of an ultrasound-contrast-agent bolus, dispersion can be indirectly estimated from the local similarity between neighboring time-intensity curves (TICs) measured by ultrasound imaging. Up until now, only linear similarity measures have been investigated. Motivated by the promising results of this approach in prostate cancer (PCa), we developed a novel dispersion estimation method based on mutual information, thus including nonlinear similarity, to further improve its ability to localize PCa. Methods: First, a simulation study was performed to establish the theoretical link between dispersion and mutual information. Next, the method's ability to localize PCa was validated in vivo in 23 patients (58 datasets) referred for radical prostatectomy by comparison with histology. Results: A monotonic relationship between dispersion and mutual information was demonstrated. The in vivo study resulted in a receiver operating characteristic (ROC) curve area equal to 0.77, which was superior (p = 0.21–0.24) to that obtained by linear similarity measures (0.74–0.75) and (p $<$ 0.05) to that by conventional perfusion parameters ($\le$0.70). Conclusion: Mutual information between neighboring time–intensity curves can be used to indirectly estimate contrast dispersion and can lead to more accurate PCa localization. Significance: An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered. [ABSTRACT FROM AUTHOR]

Background: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life.Methods/design: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires.Discussion: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE.Trial Registration: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14. [ABSTRACT FROM AUTHOR]

The limitations of the available imaging modalities for prostate cancer (PCa) localization result in suboptimal protocols for management of the disease. In response, several dynamic contrast-enhanced imaging modalities have been developed, which aim at cancer detection through the assessment of the changes occurring in the tumor microenvironment due to angiogenesis. In this context, novel magnetic resonance dispersion imaging (MRDI) enables the estimation of parameters related to the microvascular architecture and leakage, by describing the contrast agent kinetics with a dispersion model. Although a preliminary validation of MRDI on PCa has shown promising results, parameter estimation can become burdensome due the convolution integral present in the dispersion model. To overcome this limitation, in this work we provide analytical solutions of the dispersion model in the time and frequency domains, and we implement three numerical methods to increase the time-efficiency of parameter estimation. The proposed solutions are tested for PCa localization. A reduction by about 50% of computation time could be obtained, without significant changes in the estimation performance and in the clinical results. With the continuous development of new technological solutions to boost the spatiotemporal resolution of DCE-MRI, solutions to improve the computational efficiency of parameter estimation are highly required. [ABSTRACT FROM AUTHOR]

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results. [ABSTRACT FROM PUBLISHER]

The establishment of focal therapy as a valid therapy for the treatment of localized prostate cancer still faces many challenges. The rationale behind targeted ablative therapy sounds reasonably simple, directing therapy towards the predefined cancerous part of the organ while sparing uninvolved tissue; however, the execution in prostate cancer is somewhat more complicated [[5]]. We have learned that Active Surveillance is safe in patients with low-risk prostate cancer while patients with high-risk prostate cancer are best served by a multimodality approach including surgery, radiotherapy, and medical management [[1]]. [Extracted from the article]

What's known on the subject? and What does the study add? Today, angiogenesis is known to play a key role in cancer growth and development. Emerging cancer treatments are based on the suppression of angiogenesis, and modern imaging techniques investigate changes in the microvasculature that are caused by angiogenesis. As for other forms of cancers, angiogenesis is well recognised as a fundamental process in the development of prostate cancer. The novelty of this extensive report on angiogenesis in cancer, with particular attention on prostate cancer and the imaging techniques able to detect it, is the new prospective to the subject. In contrast with the other available reviews, this report goes from 'theory' to 'practice', establishing a clear link between angiogenesis development and imaged angiogenesis features. Once the key role of angiogenesis in the development of cancer and in particular prostate cancer has been fully described, attention is turned to the current imaging methods with the potential to assess the angiogenesis process and, as a consequence, to detect and localise prostate cancer. As confirmed by all available statistics, cancer represents a major clinical and societal problem in the developed world. The form of cancer with the highest incidence in men is prostate cancer. For prostate cancer, as well as for most forms of cancer, detection of the disease at an early stage is critical to reduce mortality and morbidity., Today, it is well known that pathological angiogenesis represents a crucial step in cancer development and progression. Comparable with most forms of cancer, angiogenesis also plays a fundamental role for prostate cancer growth., As a consequence, angiogenesis is an ideal target not only for novel anti-angiogenic therapies, but also for modern imaging techniques that aim at cancer localisation by detection of angiogenic microvascular changes., These techniques are mainly based on magnetic resonance, ultrasound, and nuclear imaging., This paper provides a comprehensive review of the available studies on angiogenesis in prostate cancer and its use by modern and emerging imaging techniques for prostate cancer localisation. [ABSTRACT FROM AUTHOR]

The article offers information on a study which developed in vitro propagation of human spermatogonial stem cells from small testicular biopsies to derive an adequate number of cells for successful transplantation. Testis material donated by six adult men who undergone orchidectomy as part of prostate cancer treatment was utilized during the duration of the study from April 2007 to July 2009. To determine the presence of spermatogonia and spermatogonial markers, reverse transcriptase polymerase chain reaction and immunofluorescence were applied, respectively. Main outcome measure was the propagation of spermatogonial stem cells. Also presented in details are the research findings.

OBJECTIVE To determine whether a common single nucleotide polymorphism (SNP) in the ADRA1A gene encoding the α1A-adrenoceptor modifies the short- and long-term efficacy of α1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS For 254 patients with BPH and/or lower urinary tract symptoms who received α1-adrenergic antagonists for ≥ 3 months, the ADRA1A genotype at position 1475 of the coding region was determined. The patients’ short-term response to treatment was determined for four outcome measures, i.e. the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score, peak urinary flow rate, and obstruction grade, stratified by genotype. Eventual BPH-related invasive therapy was used as the outcome for assessing the long-term response to treatment. Genetic variants at positions 834, 896, 898 and 1831 were too rare to be considered in the analysis. RESULTS There were no significant differences for the genotype strata in three of the four outcome measures. Patients with the CC genotype responded significantly better in quality-of-life perception than patients with the CT or TT genotype. There were also no significant differences in the risk of BPH-related invasive therapy among the three genotypes. CONCLUSIONS The 1475C→T SNP in the ADRA1A gene does not modify the short- and long-term efficacy of α1-adrenoceptor antagonists for treating BPH. There was a small effect on perceived quality of life but this was not reflected in other variables that measured the treatment response more directly. [ABSTRACT FROM AUTHOR]

Objectives: This multicentric clinical study was initiated to check whether percent free PSA, PSA density (PSAD) and PSA density of the transition zone (TZ-PSAD) could enhance the specificity of total PSA alone without reducing its sensitivity in the diagnosis of clinical Tlc prostate cancer by ultrasonically guided transrectal sextant biopsies in patients with a total PSA between 3 and 15 ng/ml. Patients and methods: A total of 306 patients were evaluated in seven different centres in the Netherlands and Belgium over a 2-year period. Patients with intermediate PSA levels (3.0-15 ng/ml) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and sextant biopsy under TRUS guidance. The PSAD. TZ-PSAD and percent free PSA were determined for each patient, and their relationship to prostate cancer detection was examined. Results: Identical receiver operating characteristic (ROC) curves for PSAD and TZ-PSAD could be constructed. ROC analysis showed that percent free PSA was inferior to total PSA. PSAD and TZ-PSAD in the detection of prostate cancer. Conclusion: PSAD. TZ-PSAD and percent free PSA do not enhance the specificity of total PSA for cancer detection in men with PSA values between 3 and 15 ng/ml. Each centre has to use his preferential PSA-modification. [ABSTRACT FROM AUTHOR]

The concentration of prostate-specific antigen (PSA) in serum is used as an early detection method of prostate cancer (PCa); however, it shows low sensitivity, specificity, and a poor predictive value. Initial studies suggested the glycosylation of PSA to be a promising marker for a more specific yet noninvasive PCa diagnosis. Recent studies on the molecular features of PSA glycosylation (such as antenna modification and core fucosylation) were not successful in demonstrating its potential for an improved PCa diagnosis, probably due to the lack of analytical sensitivity and specificity of the applied assays. In this study, we established for the first time a high-performance PSA Glycomics Assay (PGA), allowing differentiation of α2,6- and α2,3-sialylated isomers, the latter one being suggested to be a hallmark of aggressive types of cancer. After affinity purification from urine and tryptic digestion, PSA samples were analyzed by CE-ESI-MS (capillary electrophoresis-electrospray ionization coupled to mass spectrometry). Based on positive controls, an average interday relative standard deviation of 14% for 41 N-glycopeptides was found. The assay was further verified by analyzing PSA captured from patients' urine samples. A total of 67 N-glycopeptides were identified from the PSA pooled from the patients. In summary, the first PGA successfully established in this study allows an indepth relative quantitation of PSA glycoforms from urine. The PGA is a promising tool for the determination of potential glycomic biomarkers for the differentiation between aggressive PCa, indolent PCa, and benign prostate hyperplasia in larger cohort studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Degarelix is a gonadotropin-releasing hormone antagonist (GnRH receptor blocker) with immediate onset of action, suppressing gonadotropins, testosterone, and prostate-specific antigen (PSA) in prostate cancer. Objective: To determine the efficacy and safety of initial doses of 200mg or 240mg of degarelix and thereafter monthly subcutaneous maintenance doses of 80mg, 120mg, or 160mg of degarelix for the treatment of prostate cancer. Design, setting, and participants: The 1-yr study was of open-label, randomised design and involved 187 patients (range: 52–93 yr, median: 72 yr) with histologically confirmed adenocarcinoma of the prostate and a baseline PSA >2ng/ml. Results and limitations: At baseline, median serum testosterone was 4.13ng/ml (range: P25–P75, 3.37–5.19ng/ml) and PSA was 27.6ng/ml (range: P25–P75, 11.9–55.0ng/ml). On day 3, 88% and 92% of patients in the groups to whom 200-mg and 240-mg initial doses of degarelix were administered, respectively, had testosterone levels ≤0.5ng/ml. For patients with testosterone levels ≤0.5ng/ml at 1 mo, the testosterone levels remained ≤0.5ng/ml until the end of the study in 100% of the patients treated with a monthly maintenance dosage of 160mg of degarelix. No evidence of testosterone surge was detected. PSA decreased by 97–98% after 1 yr and the median time to 90% reduction in PSA was 8 wk in all but one patient (from the 80-mg dosage treatment group at the intial 200-mg dose of degarelix). Thirteen patients (6%) withdrew from the study due to adverse events, largely related to androgen deprivation. Conclusions: Degarelix treatment for 1 yr resulted in a fast, profound, and sustained suppression of testosterone and PSA, with no evidence of testosterone surge. Degarelix was well tolerated. [Copyright &y& Elsevier]

Abstract: Background: Focal therapy has been introduced for the treatment of localised prostate cancer (PCa). To provide the necessary data for consistent assessment, all focal therapy trials should be performed according to uniform, systematic pre- and post-treatment evaluation with well-defined end points and strict inclusion and exclusion criteria. Objective: To obtain consensus on trial design for focal therapy in PCa. Design, setting, and participants: A four-staged consensus project based on a modified Delphi process was conducted in which 48 experts in focal therapy of PCa participated. According to this formal consensus-building method, participants were asked to fill out an iterative sequence of questionnaires to collect data on trial design. Subsequently, a consensus meeting was held in which 13 panellists discussed acquired data, clarified the results, and defined the conclusions. Outcome measurements and statistical analysis: A multidisciplinary board from oncologic centres worldwide reached consensus on patient selection, pretreatment assessment, evaluation of outcome, and follow-up. Results and limitations: Inclusion criteria for candidates in focal therapy trials are patients with prostate-specific antigen <15 ng/ml, clinical stage T1c–T2a, Gleason score 3+3 or 3+4, life expectancy of >10 yr, and any prostate volume. The optimal biopsy strategy includes transrectal ultrasound-guided biopsies to be taken between 6 mo and 12 mo after treatment. The primary objective should be focal ablation of clinically significant disease with negative biopsies at 12 mo after treatment as the primary end point. Conclusions: This consensus report provides a standard for designing a feasible focal therapy trial. Patient summary: A variety of ablative technologies have been introduced and applied in a focal manner for the treatment of prostate cancer (PCa). In this consensus report, an international panel of experts in the field of PCa determined pre- and post-treatment work-up for focal therapy research. [Copyright &y& Elsevier]

Objective: Approximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with "cognitive biopsy" to confirm local recurrence of prostate cancer after RP.Materials and Methods: In this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined.Results: A total of 10 patients (mean age = 67y, mean PSA level = 3.44ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12cm (range: 0.40-2.20cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients.Conclusion: MRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes. [ABSTRACT FROM AUTHOR]