We systematically reviewed the literature on predictive factors for clinically significant prostate cancer diagnosis after prebiopsy negative magnetic resonance imaging in prostate cancer naïve ...patients.
The MEDLINE® and Scopus® databases were searched up to March 2019. The review protocol was published in the PROSPERO database (CRD42019125549). The clinical factors and markers studied were age, prostate specific antigen, prostate specific antigen isoforms, prostate specific antigen density, PCA3, prostate volume, family history, ethnicity and risk calculators. The primary objective was to determine their predictive ability for clinically significant prostate cancer diagnosis. Secondary objectives included meta-analysis of the negative predictive value of prebiopsy negative magnetic resonance imaging when combined with these predictive factors.
A total of 16 studies were eligible for inclusion. Few studies reported negative predictive value of magnetic resonance imaging combined with a marker. Prostate specific antigen density was the best studied and the strongest predictor of clinically significant prostate cancer in men with prebiopsy negative magnetic resonance imaging. There were 8 studies (1,015 patients) eligible for meta-analysis of the added value of prostate specific antigen density less than 0.15 ng/ml/ml to magnetic resonance imaging in reducing the risk of missing clinically significant prostate cancer. When combined with prostate specific antigen density, overall magnetic resonance imaging negative predictive value increased from 84.4% to 90.4% in cancer naïve patients. The increase was from 82.7% to 88.7% in biopsy naïve and from 88.2% to 94.1% in previous negative biopsy subgroups.
The use of prostate specific antigen density less than 0.15 ng/ml/ml in the presence of prebiopsy negative magnetic resonance imaging was the most useful factor to identify men without clinically significant prostate cancer who could avoid biopsy.
Purpose
To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD
®
Soluble in patients with localized prostate ...cancer (LPCa).
Methods
We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD
®
Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6.
Results
Month 6 negative biopsy rate was 68.4 % in the overall evaluable population (
N
= 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (
N
= 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function.
Conclusions
Focal VTP treatment with TOOKAD
®
Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.
Purpose:
Computerized detection of prostate cancer on T2-weighted MR images.
Methods:
The authors combined fractal and multifractal features to perform textural analysis of the images. The fractal ...dimension was computed using the Variance method; the multifractal spectrum was estimated by an adaptation of a multifractional Brownian motion model. Voxels were labeled as tumor/nontumor via nonlinear supervised classification. Two classification algorithms were tested: Support vector machine (SVM) and AdaBoost.
Results:
Experiments were performed on images from 17 patients. Ground truth was available from histological images. Detection and classification results (sensitivity, specificity) were (83%, 91%) and (85%, 93%) for SVM and AdaBoost, respectively.
Conclusions
: Classification using the authors’ model combining fractal and multifractal features was more accurate than classification using classical texture features (such as Haralick, wavelet, and Gabor filters). Moreover, the method was more robust against signal intensity variations. Although the method was only applied to T2 images, it could be extended to multispectral MR.
Purpose
To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT).
Methods
An international ...collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results.
Results
mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers.
Conclusions
The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.
The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the ...intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs.
Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests.
Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained.
Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis.
Inflatable penile prosthesis surgery is relatively rare in France, and around ten surgeons perform most of this surgery. The objective of this study was to define the learning curve concerning this ...surgery.
This study is a retrospective monocentric cohort of first time implantation of inflatable penile prosthesis between 2008 and 2016 in a university hospital. 68 consecutive patients underwent this procedure performed by a single surgeon. These patients were dispatched into two groups: a group of the first 20 patients and a group of the 48 last patients. For each patient, multiple parameters were measured including: duration of surgery, per operative complications, post operative morbidity according to Clavien classification, length of stay, and functional satisfaction. Parameters were compared using Fisher or Wilcoxon tests.
Patients were on average 58.2 year old and average operating time was 87.7minutes. The average complication rate was 16.2%. Five patients from the first group and 3 patients from the second group presented a grade 3 post operative complication according to Clavien classification. The complications included 5 infections, one erosion, one irreductible paraphimosis and a prosthesis dysfunction. This difference was statistically significative (P=0.043). The average duration of hospitalization was significantly shorter in the second group (P=0.004). There was no significative difference concerning the satisfaction using the EDITS score (P=0.52) or a Likert scale (P=0.72).
In this monocentric and retrospective study, the learning curve for first time implantation of inflatable penile prosthesis is acquired after 20 surgeries. Specific training could lower this number, but needs further evaluation.
3.
Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. ...Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours.
Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned.
We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P=3.41×10−8, N=746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours.
At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.
Purpose
To analyse the impact of the presence of extra-target non-clinically significant cancer (NCSC) after high-intensity focused ultrasound (HIFU) hemiablation on oncological results. To analyse ...radical treatment free survival (RTFS) rates at 2–3 years follow-up.
Methods
Retrospective single-centre study of 55 patients treated by primary HIFU hemiablation from 2010 to 2016. Inclusion criteria were unilateral MRI detected CSC, stage ≤ T2b, Gleason score (GS) ≤ 7, at least 6 mm distant from prostate apex. MRI with systematic and targeted biopsies was performed at diagnosis. Follow-up included clinical examination, PSA every 6 month, MRI and biopsies at 1 year and in case of PSA elevation. HIFU retreatment was possible. Whole-gland treatment was indicated in case of positive biopsies with GS ≥ 7 or maximum cancer core length > 5 mm, any GS.
Results
Mean follow-up was 33 months (SD: 17–49 months). Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS at univariate analysis (
p
= 0.29). 10 (18%) patients had a salvage whole-gland treatment after a median follow-up of 26 months (IQR 17–28). RTFS at 2 and 3 years were 92% and 80%.
Conclusion
Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS. NCSC lesion can be left untreated and actively monitored. RTFS was 80% at 3 years which support the concept of focal/partial treatment as a treatment option of CSC prostate cancer.
Abstract Purpose Over the last years, focal therapy has emerged as an intermediate management technique between radical approaches (radical prostatectomy, external beam radiation, and brachytherapy) ...and watchful waiting to manage some early stage prostate cancers (CaP). Different energy modalities are being developed. The aim of this study is to review these energy modalities and their indications. Materials and methods We reviewed the literature to concentrate on the practical aspects of focal therapy for CaP with the following key words: photodynamic therapy, high intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation, electroporation, radio frequency, external beam radiation, organ-sparing approach, focal therapy, CaP, and then by cross-referencing from previously identified studies. Results Prostatic tumor ablation can be achieved with different energies: freezing effect for cryotherapy, thermal effect using focalized ultrasound for HIFU, and using thermal effect of light for focal laser ablation (FLA) and activation of a photosensitizer by light for PDT, among others. Radio frequency and microwave therapy have been tested in this field and demonstrated their usefulness. Electroporation is currently being developed on preclinical models. External beam radiation with microboost on neoplastic foci is under evaluation. HIFU and cryotherapy require the use of sophisticated and expensive machines and, consequently, the procedure is expensive. Laser techniques seem to be less onerous, with the added advantage of size. Conclusions Several energy modalities are being developed to achieve the trifecta of continence, potency, and oncologic efficiency. Those techniques come with low morbidity but clinical experience is limited regarding to oncologic outcome. Comparison of the different focal approaches is complex owing to important heterogeneity of the trials. In the future, it seems likely that each technique will have its own selective indications.
The Montagu’s harrier (
Circus pygargus
) is a semi-colonial raptor species widely but patchily distributed across the Palearctic region with recorded cases of philopatry and presence of extra-pair ...copulation. In order to assess Montagu’s harrier spatial genetic structure and contemporary gene flow, we developed 16 new microsatellite markers using 454 pyrosequencing. Genotypes of 117 chicks sampled in a 200 × 300 km farmland area in Central Western France were analyzed to characterize genetic polymorphism at each locus and regional and fine-scale genetic structure. Fourteen markers were found polymorphic, with a number of alleles ranging from 3 to 11. The expected and observed heterozygosities ranged from 0.36 to 0.856 and from 0.35 to 0.868, respectively. A single genetic unit was found at the regional scale with higher genetic similarity observed at a small spatial scale (up to 10 km). Our results are consistent with overall large-scale juvenile and adult dispersal together with small-scale male philopatry. Cross-species amplification of this set of microsatellites makers has been successful in two closely related harrier species: the marsh harrier (
Circus aeruginosus
) and the Hen harrier (
Circus cyaneus
) for which 14 and 12 markers were polymorphic, respectively. These new microsatellite markers could be used to study the population genetic structure, contemporary gene flow and parentage analyses in these three species and to conduct microsatellite-based demographic inferences on the Montagu’s harrier.
PDF
