Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients.

Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target.

[Prostatic luminal progenitors: From tissue regeneration to therapeutic escape]. / Progéniteurs luminaux prostatiques - De la régénération tissulaire à la résistance thérapeutique.

Inhibition of androgen signaling is the gold standard treatment of benign prostate hyperplasia and prostate cancer. Despite the initial response to these treatments, therapeutic resistance is ultimately observed in most patients. Single cell RNAseq studies have shown that castration-tolerant luminal cells share several molecular and functional features with cells identified as luminal progenitor in physiological conditions. The increased prevalence of luminal progenitor-like cells in tumor contexts might result from their intrinsic androgen-independence and from the reprogramming of differentiated luminal cells into a castration-tolerant state. Thus, it is currently hypothesized that the luminal progenitor molecular profile might constitute a functional hub for cell survival in androgen deprivation context, a prerequisite for tumor regrowth. Therapeutic intervention interfering with luminal lineage plasticity is a promising approach to prevent prostate cancer progression.

Title: Progéniteurs luminaux prostatiques - De la régénération tissulaire à la résistance thérapeutique. Abstract: Les traitements médicaux de l'hyperplasie bénigne et du cancer de la prostate reposent essentiellement sur l'inhibition de la signalisation androgénique. Bien qu'initialement efficaces, ces traitements sont tôt ou tard confrontés à une résistance thérapeutique. Des données récentes de séquençage d'ARN sur cellules uniques montrent que les cellules luminales survivant à la déprivation androgénique dans ces contextes pathologiques présentent un profil moléculaire semblable à celui de cellules luminales progénitrices, présentes en faible quantité dans un contexte physiologique. Ce profil moléculaire pourrait constituer un hub de résistance à la castration et résulter, en partie, de la reprogrammation des cellules luminales tumorales. L'inhibition thérapeutique de cette plasticité cellulaire constitue une piste prometteuse pour limiter la progression du cancer prostatique.

The prognostic role of pre-cystectomy thrombocytosis in invasive bladder cancer.

PURPOSE: We aim to evaluate the impact of preoperative thrombocytosis on oncological outcomes in patients with bladder cancer (BC) who undergo radical cystectomy (RC). METHODS: Retrospective data collection of 1092 patients managed by RC for BC from 2 tertiary-care centers was performed. Elevated platelet count (PLT) was defined as > 450 × 109/L. Univariable and multivariable logistic regression analyses were used to investigate the impact of thrombocytosis on oncological outcomes. These outcomes were also compared using Kaplan-Meier survival analysis. RESULTS: The median follow-up was 50 months (32-64 months). Thrombocytosis was detected in 18.6% of the patients. The 3-year cancer-specific survival (CSS) for patients with normal PLT count was 92% which was higher than those with elevated PLT count (55%, P < 0.001). Similar results were found for the 6-year CSS with 82% for the no thrombocytosis group and 27% for the thrombocytosis group. Thrombocytosis was still significantly associated with poor prognosis for overall survival and recurrence-free survival (P < 0.001). In the multivariate analysis, CSS was significantly lower in patients with thrombocytosis (HR = 1.71, 95% CI = 1.22-2.39, P = 0.002). Patients with elevated PLT counts were also significantly more likely to receive adjuvant chemotherapy, to have a T stage > pT2b (P = 0.024), to have a positive lymph node, to have variant histology and positive resection margins, and to have concomitant carcinoma in situ (CIS) on final pathology (all P < 0.001). CONCLUSIONS: Preoperative thrombocytosis was valuable for predicting the oncological outcomes of patients undergoing RC for BC.

Native CGRP Neuropeptide and Its Stable Analogue SAX, But Not CGRP Peptide Fragments, Inhibit Mucosal HIV-1 Transmission.

Background: The vasodilator neuropeptide calcitonin gene-related peptide (CGRP) plays both detrimental and protective roles in different pathologies. CGRP is also an essential component of the neuro-immune dialogue between nociceptors and mucosal immune cells. We previously discovered that CGRP is endowed with anti-viral activity and strongly inhibits human immunodeficiency virus type 1 (HIV-1) infection, by suppressing Langerhans cells (LCs)-mediated HIV-1 trans-infection in-vitro and mucosal HIV-1 transmission ex-vivo. This inhibition is mediated via activation of the CGRP receptor non-canonical NFκB/STAT4 signaling pathway that induces a variety of cooperative mechanisms. These include CGRP-mediated increase in the expression of the LC-specific pathogen recognition C-type lectin langerin and decrease in LC-T-cell conjugates formation. The clinical utility of CGRP and modalities of CGRP receptor activation, for inhibition of mucosal HIV-1 transmission, remain elusive. Methods: We tested the capacity of CGRP to inhibit HIV-1 infection in-vivo in humanized mice. We further compared the anti-HIV-1 activities of full-length native CGRP, its metabolically stable analogue SAX, and several CGRP peptide fragments containing its binding C-terminal and activating N-terminal regions. These agonists were evaluated for their capacity to inhibit LCs-mediated HIV-1 trans-infection in-vitro and mucosal HIV-1 transmission in human mucosal tissues ex-vivo. Results: A single CGRP intravaginal topical treatment of humanized mice, followed by HIV-1 vaginal challenge, transiently restricts the increase in HIV-1 plasma viral loads but maintains long-lasting higher CD4+ T-cell counts. Similarly to CGRP, SAX inhibits LCs-mediated HIV-1 trans-infection in-vitro, but with lower potency. This inhibition is mediated via CGRP receptor activation, leading to increased expression of both langerin and STAT4 in LCs. In contrast, several N-terminal and N+C-terminal bivalent CGRP peptide fragments fail to increase langerin and STAT4, and accordingly lack anti-HIV-1 activities. Finally, like CGRP, treatment of human inner foreskin tissue explants with SAX, followed by polarized inoculation with cell-associated HIV-1, completely blocks formation of LC-T-cell conjugates and HIV-1 infection of T-cells. Conclusion: Our results show that CGRP receptor activation by full-length CGRP or SAX is required for efficient inhibition of LCs-mediated mucosal HIV-1 transmission. These findings suggest that formulations containing CGRP, SAX and/or their optimized agonists/analogues could be harnessed for HIV-1 prevention.

PLEKHS1: A new molecular marker predicting risk of progression of non-muscle-invasive bladder cancer.

Promoter mutations of pleckstrin homology domain-containing S1 (PLEKHS1) are frequent in several cancer types. To evaluate the DNA mutations, the mRNA expression and prognostic value of PLEKHS1 was evaluated in bladder cancer. We investigated DNA mutations and mRNA expression of PLEKHS1 in a first series of 154 bladder tumors [71 non-muscle-invasive bladder cancer (NMIBC) and 83 muscle-invasive bladder cancers (MIBC)] from patients who underwent transurethral bladder resection or radical cystectomy between 2001 and 2006, and 20 normal bladder samples. Results were then validated in a second series of 181 bladder tumors (91 NMIBC and 90 MIBC). All patients have signed an informed consent form. DNA mutations were analysed by high-resolution melt analysis and sanger sequencing. The mRNA expression was measured by real-time reverse-transcriptase quantitative PCR. The results of the molecular analysis were compared with survival data. PLEKHS1 mutations occurred in 25.0 and 32.2% of NMIBC and MIBC, respectively in the first series. These results were confirmed in the second series (33.0 and 37.8% of NMIBC and MIBC, respectively). In MIBC, DNA mutations were significantly more frequent with the basal than non-basal phenotype (61.5 vs. 27.1%; P=0.0025). The PLEKHS1 mRNA level was increased in 22.5 and 27.7% of NMIBC and MIBC tumors but was not associated with DNA mutations. In NMIBC, PLEKHS1 mRNA overexpression was significantly associated with progression to muscle-invasive disease (P=0.0069) and remained an independent prognostic factor on multivariate analysis (P=0.034). DNA mutations of PLEKHS1 occurred in one-third of bladder tumors and was frequent in the basal MIBC phenotype. PLEKHS1 mRNA overexpression may be an independent prognostic factor of progression-free survival in NMIBC.

Oral Pharmacologic Management of Overactive Bladder Syndrome: Where Do We Stand?

Overactive bladder syndrome (OAB) is a prevalent disorder with a significant impact on quality of life. Despite this high prevalence, there is significant underdiagnosis and undertreatment due to several barriers, including embarrassment, poor communication and low patient adherence. Currently, various antimuscarinic are available in the treatment of OAB. The introduction of mirabegron has broadened the therapeutic approach and combination therapy of both agents can be valuable in clinical practice. Yet, patient adherence to most drugs for OAB is still relatively poor. Healthcare providers need to identify and utilise strategies to improve treatment adherence by defining clear treatment goals, implement educational methods and frequently communicate with patients to identify problems with adherence. The elderly population form need special attention as in these patients, anticholinergics should be prescribed with care and adequate knowledge regarding pharmacokinetics and drug interactions in essential. Furthermore, patient expectations should be clearly discussed. In this narrative review, the current advances in oral pharmacotherapy are evaluated and the most important factors involved in the management of OAB are discussed.

Do patients have to choose between ejaculation and miction? A systematic review about ejaculation preservation technics for benign prostatic obstruction surgical treatment.

PURPOSE: Ejaculatory dysfunction is the most common side effect related to surgical treatment of benign prostatic obstruction (BPO). Nowadays, modified surgical techniques and non-ablative techniques have emerged with the aim of preserving antegrade ejaculation. Our objective was to conduce a systematic review of the literature regarding efficacy on ejaculatory preservation of modified endoscopic surgical techniques, and mini-invasive non-ablatives techniques for BPO management. METHODS: A systematic review of the literature was carried out on the PubMed database using the following MESH terms: "Prostatic Hyperplasia/surgery" and "Ejaculation", in combination with the following keywords: "ejaculation preservation", "photoselective vaporization of the prostate", "photoselective vapo-enucleation of the prostate", "holmium laser enucleation of the prostate", "thulium laser", "prostatic artery embolization", "urolift", "rezum", and "aquablation". RESULTS: The ejaculation preservation rate of modified-TURP ranged from 66 to 91%. The ejaculation preservation rate of modified-prostate photo-vaporization ranged from 87 to 96%. The only high level of evidence studies available compared prostatic urethral lift (PUL) and aquablation versus regular TURP in prospective randomized-controlled trials. The ejaculation preservation rate of either PUL or aquablation compared to regular TURP was 100 and 90 versus 34%, respectively. CONCLUSIONS: Non-ablative therapies and modified endoscopic surgical techniques seemed to be reasonable options for patients eager to preserve their ejaculatory functions.

Management of Idiopathic Overactive Bladder Syndrome: What Is the Optimal Strategy After Failure of Conservative Treatment?

CONTEXT: A considerable number of patients affected by the overactive bladder syndrome (OAB) do not respond to pharmacotherapy and bladder training due to unsatisfactory response or intolerability. OBJECTIVE: To review the available literature assessing therapeutic effect of the available third-line treatment modalities for OAB. EVIDENCE ACQUISITION: PubMed, Medline, and Cochrane databases were searched for all studies comparing outcomes of the available third-line treatment modalities for OAB. EVIDENCE SYNTHESIS: Several minimally invasive surgical procedures are available for patients with refractory OAB. These therapies include intravesical botulinum toxin type A, posterior tibial nerve stimulation, and sacral neuromodulation. CONCLUSIONS: None of the mentioned therapeutic modalities shows strong superiority over another. If the results of one therapy are not satisfactory, switching to another third-line treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns. All these factors should be taken into consideration before initiation of treatment. PATIENT SUMMARY: In the management of drug-resistant overactive bladder syndrome, the different minimally invasive treatments that are available are equal. If the results of one therapy are not satisfactory, switching to another treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns.

Impact of body mass index on the oncological outcomes of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate the association between body mass index (BMI) and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively reviewed 237 consecutive patients treated with RNU for UTUC at our institution between 1990 and 2012. Univariable and multivariable cox regression models investigated the association of BMI with disease recurrence, cancer-specific mortality, and overall mortality. RESULTS: From the 237 patients, 104 (44%) had a BMI < 25 kg/m2, 88 (37%) had a BMI between 25 and 29.9 kg/m2, and 45 (19%) had a BMI ≥ 30 kg/m2 at the time of surgery. Within a median follow-up of 44 months (IQR: 24-79), 53 patients (22.4%) experienced a disease recurrence, 85 patients (35.9%) had bladder recurrence, and 44 patients (18.6%) died from the disease. The 5 year recurrence-free and cancer-specific survival rates were, respectively, 32 and 56% for BMI ≥ 30 kg/m2, 45 and 74% for patients with BMI 25-29.9 kg/m2, and 69 and 81% for patients with BMI < 25 kg/m2. In multivariable analyses that adjusted for the effects of the standard clinico-pathological features, BMI ≥ 30 kg/m2 was associated with a higher risk of disease recurrence (HR 3.23; 95% CI 2.3-6.6, p < 0.001) and cancer-specific mortality (HR 3.84; 95% CI 2.8-6.5; p < 0.001). CONCLUSIONS: Obesity was independently associated with higher risks of disease recurrence and cancer-specific mortality in patients treated with RNU for UTUC.

Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: A retrospective study.

OBJECTIVES: Immunotherapy for bladder cancer seems to have promising results. Here, we evaluated the association between messenger RNA (mRNA) and protein levels and possible prognostic value of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immune checkpoint pathways during bladder carcinogenesis. METHODS AND MATERIALS: Tumor samples were obtained from 155 patients (84 with muscle-invasive bladder cancer [MIBC], and 71 non-muscle-invasive bladder cancer [NMIBC]) and normal bladder tissue from 15 patients. We evaluated the mRNA expression of 3 genes in the PD-1 pathway (PD-1, PD-L1, and PD-L2) and 4 in the CTLA4 pathway (CTLA4, CD28, CD80, and CD86) in normal and tumoral human bladder samples by quantitative real-time reverse transcription polymerase chain reaction, with immunohistochemistry used to evaluate the protein expression of PD-1 and PD-L1 in tumor and immune cells. Results of molecular analyses were compared with survival analyses. RESULTS: As compared with normal bladder tissue, MIBC tissue showed PD-1, PD-L1, CTLA4, and CD80 overexpression (59.5%, 60.7%, 84.5%, and 92.9%, respectively), whereas overexpression was lower in NMIBC tissue (22.5%, 4.2%, 35.2%, and 46.5%, respectively). The results of reverse transcription polymerase chain reaction analysis were confirmed by immunohistochemistry, with a high correlation between mRNA and protein expression. On multivariate analyses, overexpression of the studied genes was not associated with prognosis in relapse or progression of NMIBC or in recurrence-free and overall survival of MIBC. CONCLUSIONS: The CTLA4 pathway appears to be deregulated along with the PD-1/PD-L1 pathway in bladder carcinogenesis, with good correlation between mRNA and protein expression endorsing the useful role of immune checkpoints, especially for a large subgroup of MIBC.

Impact of body mass index on the oncological outcomes of patients treated with radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Body mass index (BMI) has been associated with worse outcomes in several solid malignancies. We aimed to evaluate the association between BMI and oncological outcomes in patients treated with radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively reviewed 701 consecutive patients treated with RC and pelvic lymphadenectomy for UCB at our institution between 1995 and 2011. Univariable and multivariable Cox regression models investigated the association of BMI with disease recurrence and cancer-specific mortality. BMI was analyzed as both continuous and categorical variable (<25 vs. 25-29 vs. ≥30 kg/m2). RESULTS: From the 701 patients, 275 (39.2 %) had a BMI < 25 kg/m2, 280 (39.9 %) had a BMI between 25 and 29.9 kg/m2, and 146 (20.9 %) had a BMI â©¾ 30 kg/m2. Within a median follow-up of 45 months (IQR 23-75), 163 patients (23.3 %) experienced a disease recurrence and 127 (18.1 %) died from the disease. In univariable analyses, BMI â©¾ 30 kg/m2 was associated with a higher risk of disease recurrence and cancer-specific mortality (both p values <0.01). In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI â©¾ 30 kg/m2 was associated with both higher risks of disease recurrence (HR 1.58; 95 % CI 1.06-2.34, p = 0.02) and cancer-specific mortality (HR 1.58; 95 % CI 1.01-2.48; p = 0.04). CONCLUSIONS: Obesity was independently associated with higher risks of disease recurrence and cancer-specific mortality in patients treated with RC for muscle-invasive UCB. BMI is a modifiable feature that may have significant individual and public health implications in patients with muscle-invasive UCB.

Are Magnetic Resonance Imaging-Transrectal Ultrasound Guided Targeted Biopsies Noninferior to Transrectal Ultrasound Guided Systematic Biopsies for the Detection of Prostate Cancer?

PURPOSE: In men with suspicion of prostate cancer the standard of cancer detection is transrectal ultrasound guided 10 to 12-core systematic biopsy. The targeted biopsy only strategy using magnetic resonance imaging-transrectal ultrasound image registration is gaining in popularity. We assessed the noninferiority of targeted vs systematic biopsy. MATERIALS AND METHODS: Between June and October 2014 a total of 108 biopsy naïve patients with prostate specific antigen between 4 and 20 ng/ml, normal rectal examination and a single suspicious image on magnetic resonance imaging were included in study at 7 centers. Patients underwent systematic biopsy by a first operator blinded to magnetic resonance imaging, immediately followed by 3 targeted biopsies within the suspicious image by a second operator. The primary end point was the cancer detection rate. The noninferiority margin was set at -5%. The secondary end points were the detection rate of clinically significant prostate cancer (maximum cancer core length 5 mm or greater for Gleason 6 or any Gleason 7 or greater disease) and procedure duration. RESULTS: Systematic and targeted biopsies detected cancer in 66 (61.1%) and 61 patients (56.5%), respectively. The mean difference was -4.5% with a 95% CI lower bound of -11.8%. A total of 13 patients with protocol violations were excluded from the per protocol analysis, which showed a mean difference of -5.2% with a 95% CI lower bound of -13.1%. Clinically significant prostate cancer was detected in 50 (46.2%) and 52 patients (48.1%) with systematic and targeted biopsies, respectively (p = 0.69). The mean ± SD duration of image fusion plus targeted biopsy was 16.7 ± 7 minutes vs 7.4 ± 3 for systematic biopsy (p <0.001). CONCLUSIONS: Targeted biopsy seemed to be inferior to systematic biopsy for overall cancer detection. Detection of clinically significant prostate cancer did not differ between targeted and systematic biopsies.

High RhoA expression at the tumor front in clinically localized prostate cancer and association with poor tumor differentiation.

Ras homolog gene family, member A (RhoA) has been reported as essential to the invasion process and aggressiveness of numerous cancers. However, there are only sparse data on the expression and activity of RhoA in clinically localised prostate cancer. In numerous cancers, tumour cells at the invasive front demonstrate more aggressive behaviour in comparison with the cells in the central regions. In the present study, the expression and activity of RhoA was evaluated in 34 paraffin-embedded and 20 frozen prostate tissue specimens obtained from 45 patients treated with radical prostatectomy for clinically localised cancer. The expression patterns of RhoA were assessed by immunohistochemical staining and western blotting. Additional comparisons were performed between the tumour centre, tumour front and distant peritumoural tissue. RhoA activity was assessed by G-LISA. Associations between RhoA expression and the clinical features and outcome of the patients were also analysed. The present study found an increasing gradient of expression from the centre to the periphery of index tumour foci. RhoA expression was significantly increased at the tumour front compared to the tumour centre, which was determined using immunohistochemistry (P=0.001). Increased RhoA expression was associated with poor tumour differentiation in the tumour front (P=0.044) and tumour centre (P=0.039). Subsequent to a median follow-up period of 52 months, the rate of prostate-specific antigen (PSA) relapse was increased in patients with higher RhoA expression at the tumour front when compared with patients with lower RhoA expression (62.5 vs. 35.0%), although the difference was not significant (P=0.09). There was no association between RhoA expression and the PSA level or pathological stage in the present study. In conclusion, RhoA expression was increased at the tumour front and was associated with poor tumour differentiation in the tumour front and tumour centre, indicating the potential role of RhoA in prostate cancer. RhoA expression may also act as a prognostic factor in prostate cancer. The present data provide a foundation for novel therapeutic approaches by targeting RhoA in prostate cancer.

Gleason Score Determination with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Guided Prostate Biopsies--Are We Gaining in Accuracy?

PURPOSE: We evaluated the accuracy of prostate magnetic resonance imaging- transrectal ultrasound targeted biopsy for Gleason score determination. MATERIALS AND METHODS: We selected 125 consecutive patients treated with radical prostatectomy for a clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to PI-RADS™ score. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. Factors associated with determining the accuracy of Gleason score on targeted biopsy were statistically assessed. RESULTS: Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Multiparametric magnetic resonance imaging detected 151 suspicious areas. Of these areas targeted biopsy showed 126 cancer foci in 115 patients, and detected the index lesion in all of them. The primary Gleason grade, secondary Gleason grade and Gleason score of the 126 individual tumors were determined accurately in 114 (90%), 75 (59%) and 85 (67%) cases, respectively. Maximal Gleason score was determined accurately in 80 (70%) patients. Gleason score determination accuracy on targeted biopsy was significantly higher for low Gleason and high PI-RADS score tumors. CONCLUSIONS: Magnetic resonance imaging-transrectal ultrasound targeted biopsy allowed for an accurate estimation of Gleason score in more than two-thirds of patients. Gleason score misclassification was mostly due to a lack of accuracy in the determination of the secondary Gleason grade.

Early results and complications of prostatic arterial embolization for benign prostatic hyperplasia.

PURPOSE: To review current knowledge on clinical outcomes and peri-operative complications of prostatic arterial embolization (PAE) in patients treated for lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). METHODS: A systematic review of the literature published from January 2008 to January 2015 was performed on PubMed/MEDLINE. RESULTS: Fifty-seven articles were identified, and four were selected for inclusion in this review. Only one randomized clinical trial compared transurethral resection of the prostate (TURP) to PAE. At 3 months after the procedure, mean IPSS reduction from baseline ranged from 7.2 to 15.6 points. Mean urine peak-flow improvement ranged from +3.21 ml/s to +9.5 ml/s. When compared to TURP, PAE was associated with a significantly lower IPSS reduction 1 and 3 months after the procedure. A trend toward similar symptoms improvement was however reported without statistical significance from 6 to 24 months. Major complications were rare with one bladder partial necrosis due to non-selective embolization. Mild adverse events occurred in 10 % of the patients and included transient hyperthermia, hematuria, rectal bleeding, painful urination or acute urinary retention. Further comparative studies are mandatory to assess post-operative rates of complications, especially acute urinary retention, after PAE and standard procedures. CONCLUSION: Early reports suggest that PAE may be a promising procedure for the treatment of patients with LUTS due to BPO. However, the low level of evidence and short follow-up of published reports preclude any firm conclusion on its mid-term efficiency. Further clinical trials are warranted before any use in clinical practice.

Real-time cancer diagnosis during prostate biopsy: ex vivo evaluation of full-field optical coherence tomography (FFOCT) imaging on biopsy cores.

OBJECTIVES: To evaluate the diagnostic accuracy (Acc) of full-field optical coherence tomography (FFOCT) for cancer detection on prostate biopsy. MATERIALS AND METHODS: Thirty-eight consecutive patients with elevated PSA and/or suspicious digital rectal examination were prospectively included. For each patient, 1-10 cores were randomly selected and imaged with FFOCT immediately after sampling. The images obtained were de-identified and analyzed by three pathologists blinded to the results of pathological evaluation. The overall average Acc was measured, as well as sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV). The Acc learning curve was assessed by multivariate logistic regression, and inter-reader concordance was assessed by Kappa index. RESULTS: One hundred and nineteen cores were imaged. Of them, 40 (33.6%) were involved with cancer. The overall average Acc of FFOCT for cancer detection was of 70.6%. Se, Sp, PPV, and NPV were of 63, 74, 55.5, and 80%, respectively. A substantial agreement was observed among pathologists (κ = 0.6, p < 0.001). On multivariate analysis, Acc was associated with the number of previously interpreted cases, with a predicted Acc of 82% at the end of learning curve. The overall average accuracy for high Gleason score (>3 + 3) determination was of 72%, although results were limited by the small amount of cases. CONCLUSIONS: FFOCT of prostate biopsy cores may provide a diagnostic accuracy greater than 80%, with a good reliability and a high NPV. TAKE HOME MESSAGE: "Full-field optical coherence tomography is a novel imaging modality that could have a potential value in real-time diagnosis of prostate cancer during prostate biopsy procedures."

Can multiparametric MRI rule in or rule out significant prostate cancer?

PURPOSE OF REVIEW: To show how multiparametric MRI can rule in the presence of significant prostate cancer (PCa), allowing for magnetic resonance-targeted biopsies to detect aggressive tumors eligible for immediate treatment and to evaluate if mp-MRI can rule out significant tumor foci to avoid overdiagnosis and overtreatment of PCa. RECENT FINDINGS: Diffusion-weighted MRI plays a major role to detect tumor foci and to rule in significant PCa. A low apparent diffusion coefficient (ADC) value indicates that high Gleason grade tumors are present. Conversely, the absence of any suspicious focus or foci with a high apparent diffusion coefficient value indicates either benign tissue or low-grade tumor SUMMARY: mp-MRI Multiparametric MRI is a highly accurate filter to detect aggressive tumors and to avoid detection of insignificant cancer. There is growing evidence that it may be indicated in any man with an elevated Prostatic Specific Antigen level before considering whether an immediate biopsy should be performed or whether a simple follow-up should be the option.

Integrated US-MR fusion images and MR targeted biopsies. What are their role and value in the detection and follow-up of prostate cancer.

Accuracy of multiparametric MRI has greatly improved the ability of localizing tumor foci of prostate cancer. This property can be used to perform a TRUS-MR image registration, new technological advance, which allows for an overlay of an MRI onto a TRUS image to target a prostate biopsy toward a suspicious area Three types of registration have been developed: cognitive-based, sensor-based, and organ-based registration. Cognitive registration consists of aiming a suspicious area during biopsy with the knowledge of the lesion location identified on multiparametric MRI. Sensor-based registration consists of tracking in real time the TRUS probe with a magnetic device, achieving a global positioning system which overlays in real-time prostate image on both modalities. Organ based registration does not aim to track the TRUS probe, but the prostate itself to compute in a 3D acquisition the TRUS prostate shape, allowing for a registration with the corresponding 3D MRI shape. The concept of an MR-US fusion TB strategy only is gaining more and more widespread acceptance. In a TB only strategy, fewer men could be biopsied overall, with a greater proportion of men diagnosed with clinically significant prostate, as well as fewer men"over diagnosed" with clinically insignificant cancer. However, more clinical research is required before this strategy is ready for widespread adoption.

Detection of significant prostate cancer with magnetic resonance targeted biopsies--should transrectal ultrasound-magnetic resonance imaging fusion guided biopsies alone be a standard of care?

PURPOSE: Magnetic resonance imaging-transrectal ultrasound fusion targeted prostate biopsies were suggested to detect significant cancer with more accuracy than systematic biopsies. In this study we evaluate the pathological characteristics of multiparametric magnetic resonance imaging detected and undetected tumor foci on radical prostatectomy specimens. MATERIALS AND METHODS: We selected 125 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to the PI-RADS score. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or tumor volume greater than 0.5 ml were considered significant. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. RESULTS: Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Of these, 137 were considered significant (Gleason score greater than 3+3 in 112) and were observed in 111 (89%) glands. A total of 95 individual tumor foci, including 14 significant foci, were missed with multiparametric magnetic resonance imaging. All of them were located in glands where another focus was detected with multiparametric magnetic resonance imaging. An additional 9 individual tumor foci, including 7 significant, were detected on multiparametric magnetic resonance imaging but missed with targeted biopsy, resulting in 5 (4%) significant cancers undetected with magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy. The magnetic resonance imaging target largest diameter was associated with high volume (greater than 0.5 cc) foci detection, while PI-RADS score and cancer involvement on targeted biopsy were associated with significant foci detection. CONCLUSIONS: In these series of men with suspicious prostate multiparametric magnetic resonance imaging findings, magnetic resonance imaging-transrectal ultrasound fusion guided targeted biopsy alone strategy would have resulted in the under detection of only 4% significant cancers.

CXCR4 is highly expressed at the tumor front but not in the center of prostate cancers.

OBJECTIVE: To evaluate the expression of CXCR4, its ligand SDF-1, ß-catenin and E-cadherin throughout the local tumor microenvironment of prostate cancer. PATIENTS AND METHODS: A total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and distant peritumoral tissue (D). Immunohistochemical analysis was used to investigate the expression patterns of CXCR4, E-cadherin and ß-catenin. Clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules' expression was statistically assessed. RESULTS: CXCR4 mRNA and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level gradually increased from the tumor center to the distant peritumoral tissue. High CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the tumor front was associated with locally advanced cancer and disease recurrence. Moreover, high CXCR4 staining at the tumor front and increased cytosolic E-cadherin expression in the same location was associated with locally advanced disease. CONCLUSIONS: CXCR4 seems overexpressed at the tumor front of prostate tumors, where it potentially promotes cell migration toward the SDF-1 centrifugal attracting gradient, as well as epithelial-mesenchymal transition. High CXCR4 and low SDF-1 levels at tumor front were both associated with adverse histological features.