Exosome Analysis in Prostate Cancer: How They Can Improve Biomarkers' Performance.

Exosomes are extracellular nanovesicles (EV), that is, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in cases of tumorigenesis open up different scenarios on their possible application to research into new biomarkers. The first purpose of the present review was to specifically analyze and compare different methodologies available for the use of exosomes in prostate cancer (PC). The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA), and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, thereby determining an increase in labor time and costs. The second purpose was to describe clinical results obtained with the analysis of PSA-expressing exosomes in PC; this provides an incredibly accurate method of discriminating between healthy patients and those with prostate disease. Specifically, the IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH). An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy controls. The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease. However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for large-scale use.

The association of impaired semen quality and pregnancy rates in assisted reproduction technology cycles: Systematic review and meta-analysis.

Some studies suggest a relationship between semen quality and pregnancy rates of assisted reproduction technologies (ART). Others have questioned the utility of semen quality as proxy for fertility in couples attempting to conceive with or without assistance. We aimed to investigate the current body of evidence which correlates semen parameters and clinical pregnancy among couples utilizing ART (i.e. in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI]) through a systematic review and meta-analysis of cross-sectional and retrospective cohort studies. Pooled Odd Ratio (OR) for oligo-, astheno- and teratospermic compared to normospermic number of ART cycles were calculated among. Meta-regression and sub-group analysis were implemented to model the contribution of clinical/demographic and laboratory standards differences among the studies. Overall, 17 studies were analysed representing 17,348 cycles were analysed. Pooled OR for impaired sperm concentration, motility and morphology was 1 (95%Confidence Interval [CI]: 0.97-1.03), 0.88 (95%CI: 0.73-1.03) and 0.88 (95%CI: 0.75-1) respectively. Further analysis on sperm morphology showed no differences with regard of IVF versus ICSI (p = 0.14) nor a significant correlation with rising reference thresholds (Coeff: -0.02, p = 0.38). A temporal trend towards a null association between semen parameters and clinical pregnancy was observed over the 20-year observation period (Coeff: 0.01, p = 0.014). The current analysis found no association between semen quality (as measured by concentration, motility or morphology) and clinical pregnancy rates utilizing ART. Future investigations are necessary to explore the association between semen parameters and other ART outcomes (e.g. fertilization, implantation, birth and perinatal health).

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed ("prostatic cancer", "albumin", "globulin", "albumin to globulin ratio") following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430−0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259−0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.

How the Analysis of the Pathogenetic Variants of DDR Genes Will Change the Management of Prostate Cancer Patients.

Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate cancer (PC) patients. The incidence of PVs in homologous recombination repair (HRR) genes among men with metastatic PC varied between 11% and 33%, which was significantly higher than that in non-metastatic PC, and BRCA2 mutations were more frequent when compared to other DDR genes. The determination of the somatic or germline PVs of BRCA2 was able to define a tailored therapy using PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) progression after first-line therapy, with significant improvements in the radiologic progression-free survival (rPFS) and overall survival (OS) rates. We propose testing all metastatic PC patients for somatic and germline HRR mutations. Somatic determination on the primary site or on historic paraffin preparations with a temporal distance of no longer than 5 years should be preferred over metastatic site biopsies. The prognostic use of DDR PVs will also be used in selected high-risk cases with non-metastatic stages to better arrange controls and therapeutic primary options. We anticipate that the use of poly-ADP-ribose polymerase (PARP) inhibitors in hormone-sensitive prostate cancer (HSPC) and in combination with androgen receptor signaling inhibitors (ARSI) will be new strategies.

Tissue Expression of Androgen Receptor Splice Variant 7 at Radical Prostatectomy Predicts Risk of Progression in Untreated Nonmetastatic Prostate Cancer.

BACKGROUND: Androgen receptor splice variant V7 (AR-V7) was recently detected in circulating tumor cells of castration-resistant prostate cancer (PC) patients and its expression correlated with resistance to new-generation androgen signaling inhibitors. OBJECTIVES: We retrospectively analyzed whether AR-V7 expression was detectable on radical prostatectomy (RP) specimens of untreated nonmetastatic PC cases, and whether it could be associated with progression after surgery. METHOD: The expression of AR-V7 and AR-FL (full length) was separately evaluated by immunohistochemistry using a streptavidin-biotin-peroxidase system with 2 anti-AR-V7 and anti-AR-FL rabbit monoclonal antibodies. RESULTS: 56 PC cases, classified by their clinical risk, were analyzed. Positive expression was found in 24/32 cases in the high-risk group, 4/13 in the intermediate-risk group, and only 2/11 in the low-risk group. We found a significant correlation between AR-V7 positivity and both risk classification (p < 0.001) and progression after surgery (p < 0.001). CONCLUSIONS: In our population of untreated nonmetastatic PC, AR-V7 is detectable by immunohistochemistry in more than 50% of cases. At this early stage, AR-V7 positivity is associated with risk classification and it can predict progression after surgery.

Prospective assessment of two-gene urinary test with multiparametric magnetic resonance imaging of the prostate for men undergoing primary prostate biopsy.

PURPOSE: To evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) in predicting prostate cancer (PCa) and clinically significant PCa (csPCa) on prostate biopsies among men scheduled for initial prostate biopsy. METHODS: In this single-center prospective study, 52 men scheduled for initial prostate biopsy, based on elevated total PSA level (> 3 ng/ml) or abnormal digital rectal examination, were consecutively included. All subjects underwent SelectMDx, PSA determination and mpMRI. RESULTS: SelectMDx score was positive in 94.1 and 100% of PCa and csPCa, respectively, and in only 8.6% of negative cases at biopsy. The probability for a csPCa at the SelectMDx score was significantly (p = 0.002) higher in csPCa (median value 52.0%) than in all PCa (median value 30.0%). SelectMDx showed slightly lower sensitivity (94.1 versus 100.0%) but higher specificity (91.4%) than total PSA (17.1%), and the same sensitivity but higher specificity than mpMRI (80.0%) in predicting PCa at biopsy. The association of SelectMDx plus mpMRI rather than PSA density (PSAD) plus mpMRI showed higher specificity (both 91.4%) compared to the association of PSA plus mpMRI (85.7%). In terms of csPCa predictive value, SelectMDx showed higher specificity (73.3%) than PSA (13.3%) and mpMRI (64.4%); as for the association of SelectMDx plus mpMRI (75.6%) versus PSA plus mpMRI (68.9%), the association of PSAD plus mpMRI showed the highest specificity (80.0%). CONCLUSION: Our results of SelectMDx can be confirmed as significant but their impact on clinical practice together with a cost-effectiveness evaluation should be investigated in a larger prospective multicenter analysis.

A biofeedback-guided programme or pelvic floor muscle electric stimulation can improve early recovery of urinary continence after radical prostatectomy: A meta-analysis and systematic review.

PURPOSE: Urinary incontinence (UI) after radical prostatectomy (RP) is an early side effect after catheter removal. This systematic review and meta-analysis were conducted to compare different forms of non-invasive treatments for post-RP UI and to analyse whether the addition of biofeedback (BF) and/or pelvic floor muscle electric stimulation (PFES) to PF muscle exercise (PFME) alone can improve results in terms of continence recovery rate. MATERIALS AND METHODS: A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across subgroups during a 12-months follow-up. RESULTS: Twenty-six articles were selected. At baseline after RP and catheter removal, mean pad weight varied extremely. At 1- and 3-months intervals, mean difference in pad weight recovery from baseline was significantly higher using guided programs (BF, PFES or both) than using PFME alone (3-months: PFME 111.09 g (95%CI 77.59-144.59), BF 213.81 g (95%CI -80.51-508-13), PFES 306.88 g (95%CI 158.11-455.66), BF + PFES 266.31 g (95%CI 22.69-302.93); P < .01), while at 6- and 12-months differences were similar (P > .04). At 1- and 3-months intervals, event rate (ER) of continence recovery was significantly higher using guided programs than using PFME alone (3-months: PFME 0.40 (95%CI 0.30-0.49), BF 0.49 (95%CI 0.31-0.67), PFES 0.57 (95%CI 0.46-0.69), BF + PFES 0.75 (95%CI 0.60-0.91); P < .01), while at 6- and 12-months ERs were similar. CONCLUSIONS: Regarding non-invasive treatment of UI secondary to RP, the addition of guided programs using BF or/and PFES demonstrated to improve continence recovery rate, particularly in the first 3-month interval, when compared with the use of PFME alone.

Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison.

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65-97) vs. 65 (51-75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes.

Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.

Predictors of Hospitalization After Ureteroscopy Plus Elective Double-J Stent as an Outpatient Procedure.

PURPOSE: To evaluate the safety and feasibility of ureteroscopy plus elective double-J stent as an outpatient procedure in an unselected population with regard to the treatment for ureteral calculi and to present a multivariate analysis of factors predict hospitalization. MATERIALS AND METHODS: Ureteroscopy was performed as an outpatient procedure on 308 consecutive patients with ureteral stones. Contraindication for day case surgery was the only exclusion criteria from the study. All causes that led to immediate hospitalization were recorded; at the same time, all causes of hospitalization that occurred within 72 h from the procedure were also recorded and included in the final analysis. RESULTS: The overall stone-free rate and the rate of hospitalization were 94.5 and 9.7% respectively. Intraoperative complications were observed in 16 patients (5.1%). In terms of the variables related to hospitalization, the univariate analysis showed a statistical significant association between the American Society of Anesthesiologists (ASA) score (p < 0.001) and operative time (p = 0.018). At multivariate analysis, the only independent factor predictor of hospitalization was the ASA score (p < 0.001). CONCLUSIONS: In our experience, semirigid ureteroscopy is a safe and effective treatment that is independent of intraoperative local conditions or stone size. Elective Double-J stenting avoids major complications as the first reason for hospitalization. We suggest that ASA score > 2 should be taken into account when ureterorenoscopy is planning as an outpatient procedure.

Psychological impact of different primary treatments for prostate cancer: A critical analysis.

Limited attention has been given to the psychological impact of primary treatments in patients with prostate cancer. Aim of our analysis was to critically analyse the current evidence on the psychological impact of different primary treatments (surgery, radiotherapy and active surveillance), in patients with prostate cancer, using validated questionnaires. We searched in the MEDLINE and Cochrane library database from the literature of the past 15 years (primary fields: prostate neoplasm, AND radical prostatectomy or radiotherapy or active surveillance AND psychological distress or anxiety or depression; secondary fields: urinary, sexual, bowel modifications, non-randomised and randomised trials). Overall eighteen original and review articles were included and critically evaluated. Either radical prostatectomy or active surveillance and radiotherapy are well-tolerated in terms of definite anxiety and depression during the post-treatment follow-up. A mutual influence between functional and psychological modifications induced by treatments has been demonstrated. Urinary symptoms related to incontinence more than sexual and bowel dysfunction are able to induce psychological distress worsening. In conclusion, patients and their clinicians might wish to know how functional and psychological aspects may differently be influenced by treatment choice.

Oral ethinylestradiol in castration-resistant prostate cancer: a 10-year experience.

OBJECTIVES: To describe our 10-year experience with the use of oral ethinylestradiol in the treatment of metastatic castration-resistant prostate cancer. METHODS: From February 2000 to April 2010, 116 patients with a metastatic castration-resistant prostate cancer were prospectively submitted to oral ethinylestradiol monotherapy. Inclusion criteria were: diagnosis of castration-resistant prostate cancer after failure of at least two lines of androgen deprivation therapy and radiological evidence of metastases. Exclusion criteria were: symptomatic cases with a European Cooperative Oncology Group score >2 and severe or uncontrolled cardiovascular diseases. At inclusion in the study, all patients discontinued the previous androgen deprivation therapy and started oral ethinylestradiol at the daily dose of 1 mg. Aspirin (100 mg/daily) was concomitantly given. RESULTS: The median ethinylestradiol therapy duration was 15.9 months (range 8-36 months), whereas the median follow up of patients was 28 months (range 13-36 months). During ethinylestradiol therapy, a confirmed prostate-specific antigen response was found in 79 patients (70.5%). The median time to prostate-specific antigen progression was 15.10 months (95% confidence interval 13.24-18.76 months). A toxicity requiring treatment cessation was observed in 26 patients (23.2%) at a median time of 16 months (mainly thromboembolism). CONCLUSIONS: Our 10-year experience shows that ethinylestradiol provides a prostate-specific antigen response in a high percentage of patients with metastatic castration-resistant prostate cancer. Cardiovascular toxicity can be managed through accurate patient selection, close follow up and a concomitant anticoagulation therapy.

Diagnostic Accuracy of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Muscle-Invasive Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a diagnostic tool that is gaining popularity for its ability to improve overall diagnostic accuracy in bladder cancer (BC) staging. Our aim is to determine the cumulative diagnostic performance of CEUS in predicting preoperative muscle invasiveness using a comprehensive systematic review and pooled meta-analysis. METHODS: A systematic review until October 2023 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patients with BC suspicion were offered CEUS before the transurethral resection of the bladder tumor (TURBT). The diagnostic performance of CEUS was evaluated based on non-muscle-invasive bladder cancer (NMIBC) vs. muscle-invasive bladder cancer (MIBC) confirmed at the final histopathological examination after TURBT. The outcomes were determined through pooled sensitivity, specificity, pooled positive likelihood ratio (PLR+), negative likelihood ratio (PLR-), and area under the summary receiver operating characteristic (SROC) along with their respective 95% confidence intervals (CI). RESULTS: Overall, five studies were included. In these studies, a total of 362 patients underwent CEUS prior to TURBT. The pooled sensitivity and specificity were 0.88 (95% CI: 0.81-0.93) and 0.88 (95% CI: 0.82-0.92), respectively. SROC curve depicted a diagnostic accuracy of 0.94 (95% CI: 0.81-0.98). The pooled PLR+ and PLR- were 7.3 (95% CI: 4.8-11.2) and 0.14 (95% CI: 0.08-0.23), respectively. CONCLUSIONS: Our meta-analysis indicates that CEUS is highly accurate in the diagnosis and staging for BC. Beyond its accuracy, CEUS offers the advantage of being a cost-effective, safe, and versatile imaging tool.

An untargeted analytical workflow based on Kendrick mass defect filtering reveals dysregulations in acylcarnitines in prostate cancer tissue.

BACKGROUND: Metabolomics is nowadays considered one the most powerful analytical for the discovery of metabolic dysregulations associated with the insurgence of cancer, given the reprogramming of the cell metabolism to meet the bioenergetic and biosynthetic demands of the malignant cell. Notwithstanding, several challenges still exist regarding quality control, method standardization, data processing, and compound identification. Therefore, there is a need for effective and straightforward approaches for the untargeted analysis of structurally related classes of compounds, such as acylcarnitines, that have been widely investigated in prostate cancer research for their role in energy metabolism and transport and ß-oxidation of fatty acids. RESULTS: In the present study, an innovative analytical platform was developed for the straightforward albeit comprehensive characterization of acylcarnitines based on high-resolution mass spectrometry, Kendrick mass defect filtering, and confirmation by prediction of their retention time in reversed-phase chromatography. In particular, a customized data processing workflow was set up on Compound Discoverer software to enable the Kendrick mass defect filtering, which allowed filtering out more than 90 % of the initial features resulting from the processing of 25 tumoral and adjacent non-malignant prostate tissues collected from patients undergoing radical prostatectomy. Later, a partial least square-discriminant analysis model validated by repeated double cross-validation was built on the dataset of 74 annotated acylcarnitines, with classification rates higher than 93 % for both groups, and univariate statistical analysis helped elucidate the individual role of the annotated metabolites. SIGNIFICANCE: Hydroxylation of short- and medium-chain minor acylcarnitines appeared to be a significant variable in describing tissue differences, suggesting the hypothesis that the neoplastic growth is linked to oxidation phenomena on selected metabolites and reinforcing the need for effective methods for the annotation of minor metabolites.

Mid-term outcomes of minimally invasive infrapubic approach for inflatable penile prosthesis implantation: A single-center study and literature review.

BACKGROUND: The minimally invasive infrapubic approach (MIIA) for inflatable penile prosthesis (IPP) placement has shown favorable peri-operative safety and efficacy profile, but scarce data exist on long-term follow-up. OBJECTIVES: We investigated the safety and efficacy of IPP implantation via the MIIA after a minimum 5-year follow-up. MATERIALS AND METHODS: We identified data of implanted patients prospectively included in our institutional database. Complications and functional outcomes were assessed by using validated tools. Specifically, quality of life and patient satisfaction were evaluated by the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Kaplan-Meier method was used to analyze IPP survival (defined as a working IPP). RESULTS: Overall, 67 patients implanted by MIIA with a median (IQR) age of 64 years (61-70) were included. The median (IQR) follow-up duration was 71 months (63-80). Fifteen (22%) patients experienced complications: minor (Clavien ≤2) events included changes in penile sensitivity (n = 1; 1.5%), orgasmic dysfunction (n = 1; 1.5%), pain (n = 5; 7%), urinary tract infection (n = 2; 3%), and chronic discomfort (n = 1; 1.5%); major (Clavien 3) complications were represented by mechanical failure (n = 3; 4.5%), IPP infection (n = 1; 1.5%), and cylinder protrusion (n = 1; 1.5%). The estimated IPP survival was 94% (95% CI, 91.4-96.6), 92.5% (95% CI, 89.7-95.3), and 92.5% (95% CI, 89.7-95.3) at 3, 5, and 7 years after implantation, respectively. In patients using the device at follow-up (n = 61; 91%), median (IQR) scores for QoLSPP domains demonstrated favorable functional outcomes and patient satisfaction: functional 21 (19-23), personal 16 (15-18), relational 14 (12-15), and social 12 (11-14). DISCUSSION AND CONCLUSION: This study represents the longest follow-up using validated tools to assess the outcomes of IPP implantation via MIIA so far. IPP placement via MIIA confirms to be safe and to offer high satisfaction to both patients and partners at mid-term evaluation.

Intermittent Versus Continuous Androgen Deprivation Therapy for Biochemical Progression After Primary Therapy in Hormone-Sensitive Nonmetastatic Prostate Cancer: Comparative Analysis in Terms of CRPC-M0 Progression.

INTRODUCTION: To analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). PATIENTS: 170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. METHODS: we retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. RESULTS: no significant (P= .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P= .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). CONCLUSIONS: in our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists.

Systematic review and meta-analysis of serum total testosterone and luteinizing hormone variations across hospitalized Covid-19 patients.

A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary-gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n = 18 series with n = 1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (- 3.25 nmol/L, 95%CI - 0.57 and - 5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (- 5.04 nmol/L, 95%CI - 1.26 and - 8.82) but similar for Covid-19 survivors and non-survivors (- 3.04 nmol/L, 95%CI - 2.04 and - 4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer: A meta-analysis and systematic review.

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: -0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy.

Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification into low- and high-risk cases for early progression in metastatic disease is necessary. At present, PSA-DT represents the best parameter to define low- and high-risk BCR PC, but real precision medicine is strongly suggested to define tailored management for patients with BCR. Before defining management, it is necessary to exclude the presence of low-volume metastasis associated with PSA progression using new-generation imaging, preferably with PSMA PET/CT. Low-risk BCR cases should be actively observed without early systemic therapies. Early treatment of low-risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such as the development of castration resistance before the appearance of metastases (non-metastatic castration-resistant PC). Patients with high-risk BCR benefit from early systemic therapy. Even with overall survival (OS) as the primary treatment endpoint, metastasis-free survival (MFS) should be used as a surrogate endpoint in clinical trials, especially in long survival stages of the disease. The EMBARK study has greatly influenced the management of high-risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSIs) and ADT combination therapy. In high-risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining an unchanged quality of life in the asymptomatic phase of the disease. The possibility of using ARSIs alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than with the intensification of the combination therapy. Continued use versus discontinuation of enzalutamide plus leuprolide intensified therapy upon reaching undetectable PSA levels needs to be better defined with further analysis. Real-world analysis must verify the significant results obtained in the context of a phase 3 study.

Thulium laser supported nephron sparing surgery for renal cell carcinoma.

PURPOSE: We analyze the feasibility, advantages and results of the use of a thulium laser in nephron sparing surgery for renal cell carcinoma. MATERIALS AND METHODS: In this single center prospective study 10 consecutive high risk patients underwent open or laparoscopic thulium laser assisted enucleation for small peripheral renal cell carcinoma at our department. We used a 2.0 µm continuous or pulsed thulium laser. This diode pumped solid state laser emits a wavelength of 2,013 nm in the infrared spectrum and penetrates tissue to a depth of 0.5 mm. RESULTS: The entire tumor enucleation was performed using the frontal thulium laser fiber. In all cases the thulium laser produced a smooth incision of the renal parenchyma and a safe delineation of the plane between the tumor and the surrounding tissue. In addition, in the off clamp procedures bleeding was limited during the dissection and did not interfere with the definition of the surgical plane. Median surgical time from the beginning of the laser assisted tumor dissection to the end, after verification of bleeding control on the cut surface, was 15 minutes (range 12 to 20). No significant (less than 40 cc) blood loss occurred during the laser assisted tumor dissection. All cases were clear cell renal cell carcinoma and no positive surgical margins were found. In all cases postoperative management was uncomplicated without evidence of hemorrhage. CONCLUSIONS: In our prospective preliminary experience, thulium laser assisted enucleation for renal cell carcinoma is a feasible, safe and effective procedure.