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.

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.

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.

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.

Influence of statin use on clinicopathological characteristics of localized prostate cancer and outcomes obtained after radical prostatectomy: a single center study.

INTRODUCTION: To assess the impact of statin use on biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP). MATERIALS AND METHODS: Data from all men treated with robot-assisted laparoscopic RP (RALRP) for localized prostate cancer between 2009 and 2014 at our institution were prospectively collected: age, body mass index (BMI), statin-use status, preoperative prostate-specific antigen (PSA) level, clinical T stage, biopsy Gleason score (bGS), D'Amico risk group, pathological T stage, specimen Gleason score (sGS), multifocality, peri neural invasion, positive surgical margins and time to BCR. Univariate and multivariate analysis were performed to test associations between statin use and prognostic factors of prostate cancer and/or BCR. RESULTS: Overall, 591 patients with a median follow up of 42.3 months [25.8-59.9] were included in the current study and split in two cohorts: statin users (n = 156) and statin non-users (n = 435). When comparing statin user and non-users, no significant difference was found in terms of clinical, biochemical and pathological characteristics except for BMI (median 29 versus 26, respectively; p = 0.04). Regarding BCR, there was no significant difference between men using statin versus those not using them (4.5% versus 4.6%, p = 0.65). In univariate analysis, statin use was not significantly correlated to any prognostic factors of prostate cancer recurrence. Furthermore, there was no significant difference in the 5 years biochemical-free survival rates between statin users and non-users (75% versus 73%; p = 0.7). CONCLUSIONS: From the current study, statin daily intake was not significantly associated with any prognostic factors of prostate cancer and with BCR after RARLP.

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.

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.

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.

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.

Is It Time to Anticipate the Use of PARP Inhibition in Prostate Cancer Patients?

The increasing diffusion of genetic analysis regarding the pathogenetic variants (PVs) of genes involved in DNA Damage Repair (DDR) mechanisms and the development of Poly ADP ribose polymerase (PARP) inhibitors (PARPis) led to the first valid precision medicine option tailored toward metastatic prostate cancer (mPC). The concept of anticipation in the systemic treatment of mPC was initially adopted for androgen receptor signaling inhibitors (ARSIs) to describe the expansion of their indications, from the setting of the late-stage second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) to first-line therapy in selected cases. There is already mounting evidence in favor of the anticipation of PARPis in the first line of mCRPC therapy, and further evidence in favor of mHSPC is emerging. Many studies have demonstrated the synergism between ARSIs and PARP inhibitors. Recent discoveries regarding the crosstalk between the androgen receptor (AR) and DNA repair mechanisms are disconnecting the use of PARPis from genetic analysis. The new message emerging is that the combination of PARPis with ARSIs may work independently of DDR mutational status. As a matter of fact, most of the recent trials analyzing the combination of PARPis with abiraterone or enzalutamide as a first-line therapy enrolled mCRPC patients irrespective of their mutational status. The PROPEL trial concluded that the advantage of the combination was independent of PV status, despite a higher advantage being reported in the BRCA1/2 mutated subgroup. The MAGNITUDE trial, however, showed a significant advantage only in the DDR mutated subgroup, and the DDR non-mutated cohort was closed for further enrollment. The combination of PARPis with ARSIs represents a significant strategy with a view to the anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR genes.

Regenerative Medicine-Based Treatment of Stress Urinary Incontinence with Mesenchymal Stem Cells: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis is to analyze clinical trials on the use of autologous stem cell [SC] injection for the treatment of stress urinary incontinence [SUI] in humans. METHODS: We analyzed the effect in terms of UI improvement and continence recovery after treatment. A literature search was performed following the PRISMA guidelines. Entry into the analysis was restricted to data collected from clinical prospective trials on humans, including female and male patients with SUI. We performed a cumulative meta-analysis to explore the trend in the effect size across different groups at follow-up. Available data were compared in terms of Event Rate [ER] for the percentage of pad-free patients. RESULTS: 12 trials were enclosed in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived stem cells [MDSCs] were used in 9 and adipocyte- derived SCs [ADSC] in 3 trials. Considering a random effect model, ER of continence recovery was 0.41 [95%CI 0.29 - 0.54], with similar results between the ADSC [ER, 0.40;95%CI 0.12 - 0.69] and the MDSC group [ER 0.41; 95%CI 0.27-0.55] [I2 84.69%; Q 104.69 - p<0.01] [Test of group differences p=0.96]. CONCLUSION: Autologous MDSC or ADSC injection to treat SUI is demonstrated to be a safe procedure and a 41% mean rate of continence recovery is described. A higher effort should be produced to design better clinical trials, objectively evaluating either modifications inside the urethral sphincter or long-term functional results in terms of pad test and UI questionnaires.

Translation and validation of the Italian version of the Wisconsin Stone Quality of Life Questionnaire (I-WISQOL) for assessing quality of life in patients with urolithiasis.

BACKGROUND: Urolithiasis is a chronic condition, and it has been associated with a significant negative impact on patients' health-related quality of life (HRQOL). Several tools to assess patients' HRQOL have been validated in Italian, however disease-specific HRQOL instruments are still lacking. We aimed to develop and validate the Italian version of the WISQOL (I-WISQOL) in patients with urolithiasis. METHODS: The Italian version of the WISQOL was developed in a multistep process involving primary translation, back-translation, and pilot testing among a group of patients (N.=10). Patients presenting with urolithiasis were prospectively recruited from the outpatient stone clinics and completed both questionnaire WISQOL and SF-36. Demographic information, as well as medical and surgical data, were obtained through an interview. Internal consistency of the I-WISQOL was obtained with Cronbach's α. Correlation of total scores of the I-WISQOL and SF36 was assessed to determine convergent validity using Spearman Rho. Correlations between clinical variables and results from the I-WISQOL were analyzed to descriptively assess the association of interest. RESULTS: A total of 93 participants were evaluated and completed the Italian version of the I-WISQOL. The I-WISQOL demonstrated excellent internal consistency (Cronbach's α 0.95) and good convergent validity with the validated SF-36 (Spearman Rho r=0.70, P<0.001). Using ANOVA analysis, a significant decline in WISQOL Score was noted with the increasing number of renal colics (P=0.0543), ER visits (P=0.037), number of inpatient hospitalization (P=0.025). At multivariate analysis, worse WISQOL total score was predicted by a greater number of renal colic events (ß=-4.92 [-8.81-1.04], P=0.014) and by a greater number inpatient hospitalization (ß=-7.31 [-14.35 -0.26], P=0.042). CONCLUSIONS: The I-WISQOL is an internally consistent and valid instrument to assess HRQOL in Italian-speaking patients with kidney stones. Its use in clinical practice should be implemented in order to tailor the management of each patient.

Multiparametric magnetic resonance imaging of the prostate can improve the predictive value of the urinary prostate cancer antigen 3 test in patients with elevated prostate-specific antigen levels and a previous negative biopsy.

UNLABELLED: Study Type--Clinical (prospective trial) Level of Evidence 2b. What's known on the subject? and What does the study add? In clinical practice, we know that it is necessary to identify new biomarkers that can better detect prostate cancer (PC), at the same time as reducing the number of unnecessary biopsies. Recently, studies have suggested that the most relevant clinical scenario in which the prostate cancer antigen 3 (PCA3) score could be used comprises patients with a previous negative prostate biopsy and persistently elevated PSA levels. At the same time, although multiparametric MRI is not currently used as a first approach for diagnosing PC, it can be useful for directing targeted biopsies, especially in those patients with elevated PSA levels and a previous negative TRUS-guided biopsy. Considering all of these aspects, the present study aimed to evaluate the role of multiparametric MRI as an additional diagnostic tool for improving the accuracy of the urinary PCA3 test in patients with increased PSA levels and a previous negative prostate biopsy. Our hypothesis is that the potential value of the PCA3 test as a biomarker for PC diagnosis could be improved by the use of multiparametric MRI in directing prostate biopsy. In the present study, we show that, in cases with a previous negative biopsy and persistently elevated PSA levels submitted to multiparametric MRI to direct biopsies, the sensitivity of the PCA3 test significantly improved (79% vs 68%). However, further larger randomized studies on this combination using a new biomarker and a new imaging modality for PC diagnosis are expected. OBJECTIVE: • To evaluate the role of multiparametric magnetic resonance imaging (MRI) as an additional diagnostic tool for improving the accuracy of the urinary prostate cancer antigen 3 (PCA3) test in patients with an increase in prostate-specific antigen (PSA) levels and a previous negative prostate biopsy. PATIENTS AND METHODS: • The present study comprised a prospective randomized study on patients with a previous negative transrectal ultrasonography (TRUS)-guided prostate biopsy and elevated PSA levels. • In total, 180 cases were analyzed, and all were submitted to PCA3 assay. • Patients in group A were submitted to a second random TRUS-guided prostate biopsy, whereas patients in group B were submitted to a multiparametric MRI examination and then to a second TRUS-guided prostate biopsy. RESULTS: • At the second biopsy, a histological diagnosis of prostate cancer was found in 26 of 84 cases (30.9%) in group A and in 29 of 84 cases (34.5%) in group B. • In group A, the sensitivity and specificity of the PCA3 score were 68.0% and 74.5% respectively (positive predictive value of 53.1%, negative predictive value of 84.6% and accuracy of 72.6%). • In group B, the sensitivity and specificity of the PCA3 score were 79.3% and 72.7%, respectively (positive predictive value of 60.5%, negative predictive value of 86.9% and accuracy of 75.0%). • For the PCA3 score, the area under the receiver-operator characteristic curve was 0.825 (95% confidence interval, 0.726-0.899) in group A and 0.857 (95% confidence interval, 0.763-0.924) in group B (P < 0.001). CONCLUSION: • In patients with a previous negative biopsy and persistently elevated PSA levels, the use of multiparametric MRI for indicating sites suitable for rebiopsy can significantly improve the sensitivity of the PCA3 test in the diagnosis of prostate cancer.

Use of multiparametric MR with neurovascular bundle evaluation to optimize the oncological and functional management of patients considered for nerve-sparing radical prostatectomy.

INTRODUCTION: To obtain the best results with radical prostatectomy, either from an oncological or a functional point of view, a correct selection of cases and planning of surgery are crucial. Multiparametric magnetic resonance imaging (MRI) promises to make it a successful imaging tool for improving many aspects of prostate cancer management. AIM: The aim of this study is to evaluate whether a modern multiparametric MRI can help either to better select prostate cancer cases for a nerve-sparing radical prostatectomy or to improve the functional evaluation related to neurovascular bundles preservation. MAIN OUTCOME MEASURES: The effect of preoperative MRI on neurovascular bundle management was examined for the frequency and the appropriateness of changes of the surgical plane on the basis of MRI indications. METHODS: In a prospective study, 125 consecutive patients with biopsy proven prostate cancer who were scheduled to undergo bilateral nerve-sparing surgery. All patients included into the study were submitted to a preoperative multiparametric MRI. On the basis of MRI evaluation, patients were divided into two groups. Patients in group A were then submitted to a bilateral nerve-sparing (NS) radical prostatectomy (RP), whereas patients in group B were submitted to unilateral NS or non-NS RP. RESULTS: In group A, the confirmation from the MRI study to perform a bilateral NS procedure was appropriate in 70 of 73 cases (95.9%), whereas in group B, the surgical plan was appropriate in 28 of 32 cases (87.5%). On the contrary, MRI findings suggested a change in the initial surgical plan (group B) for 32 of 105 cases (30.5%). Of these 32 cases in group B, MRI suggested to perform a unilateral NS procedure in 21 of 32 cases (65.6%) and a non-NS procedure in 11 of 32 cases (34.4%). CONCLUSIONS: Multiparametric MRI analysis can significantly improve the standard selection and management of prostate carcinoma cases considered for an NS RP.

Comparison of Different Invasive Devices for the Treatment of Urinary Incontinence after Radical Prostatectomy.

Purpose: To compare different forms of invasive treatments for postradical prostatectomy (RP) urinary incontinence (UI) in terms of quantitative and qualitative parameters and continence recovery rate. Methods: We distinguished five categories of treatment: A = bulking agents, B = fixed slings, C = adjustable slings, D = circumferential compressor devices (artificial sphincter), and E = noncircumferential compressor devices (ProACT). A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across groups at postoperative follow-up. We compared the available treatment arms using standardized mean difference (SMD) and event rate (ER) for questionnaire results, number of pads/day, and percentage of pad-free patients. Evidence synthesis. 36 clinical trials were selected. At baseline, in the different populations, mean number of pad-day varied from 1.1 to 8.8, 24-hour pad weight varied extremely from 17.3 g to 747.0 g, and mean ICIQ-UI-SF questionnaire score varied from 4.8 to 18.6. Considering a random effect model among eligible studies, ER of continence recovery was 0.33 (95% CI -0.12-0.78), 0.63 (95% CI 0.55-0.71), 0.65 (95% CI 0.58-0.72), 0.50 (95% CI 0.34-0.66), and 0.53 (95%CI 0.36-0.70), respectively, in groups A, B, C, D, and E (I 2 85.87%; Q 249.82-P > 0.01) (test of group differences P=0.22). Conclusion: In our analysis, the use of adjustable and fixed slings is associated with the highest whereas the use of bulking agents is associated with the lowest recovery rate of continence after treatment. Results are conditioned by an elevated rate of heterogeneity in part explained with a high variability of consistence in urinary leakage at baseline among populations.

Which factors can influence post-operative renal function preservation after nephron-sparing surgery for kidney cancer: a critical review.

Introduction: The aim of this article was to compare different surgical approaches to perform nephron-sparing surgery (NSS) in terms of preservation of renal function. Material and methods: We critically reviewed the literature from January 2000 to December 2020 including studies comparing different surgical techniques. Results: A total of 51 studies met the inclusion criteria. Functional outcomes were evalutated in terms of percentual change of estimated glomerular filtration rate (eGFR) and impaired renal function (IRF) on scintigraphy. In cases with a mean age <60 years, the mean decrease in eGFR after NSS was 11.7% and that of IRF 10.0%, whereas higher changes were found in cases with a mean age ≥60 years. For open NSS, the mean eGFR and IRF changes were 15.3% and 21.1%, respectively; using the laparoscopic approach, the mean percentual eGFR and IRF changes were 13.9% and 11.1%, respectively; in robotic cases, the mean eGFR and IRF changes were 10.8% and 13.1%, respectively. In cases performed with global ischemia, the mean eGFR and IRF changes were 12.7% and 15.1%, respectively. Similar results were found distinguishing ischemia time ≤20 and >20 minutes, whereas using the off-clamp technique the mean decreases in eGFR and IRF were only 4.2% and 6%, respectively. Conclusions: Patients' age, tumor size, off-clamp technique, and robot-assisted approach were significant independent predictive factors able to influence renal function changes after NSS. A lower reduction of eGFR and IRF after NSS was reported in patients aged <60 years, submitted to a robot-assisted procedure, and using selective and cold ischemia <20 minutes or an off-clamp technique.

Comparative Prospective and Longitudinal Analysis on the Platelet-to-Lymphocyte, Neutrophil-to-Lymphocyte, and Albumin-to-Globulin Ratio in Patients with Non-Metastatic and Metastatic Prostate Cancer.

PURPOSE: To prospectively evaluate the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) diagnostic and prognostic predictive value in a stratified population of prostate cancer (PC) cases. METHODS: Population was divided based on the clinical and histologic diagnosis in: Group A: benign prostatic hyperplasia (BPH) cases (494 cases); Group B: all PC cases (525 cases); Group B1: clinically significant PC (426 cases); Group B2: non-metastatic PC (416 cases); Group B3: metastatic PC (109 cases). NLR, PLR, and AGR were obtained at the time of the diagnosis, and only in cases with PC considered for radical prostatectomy, determinations were also repeated 90 days after surgery. For each ratio, cut-off values were determined by receiver operating characteristics curve (ROC) analysis and fixed at 2.5, 120.0, and 1.4, respectively, for NLR, PLR, and AGR. RESULTS: Accuracy in predictive value for an initial diagnosis of clinically significant PC (csPC) was higher using PLR (0.718) when compared to NLR (0.220) and AGR (0.247), but, despite high sensitivity (0.849), very low specificity (0.256) was present. The risk of csPC significantly increased only according to PLR with an OR = 1.646. The percentage of cases with metastatic PC significantly increased according to high NLR and high PLR. Accuracy was 0.916 and 0.813, respectively, for NLR and PLR cut-off, with higher specificity than sensitivity. The risk of a metastatic disease increased 3.2 times for an NLR > 2.5 and 5.2 times for a PLR > 120 and at the multivariate analysis. CONCLUSION: PLR and NLR have a significant predictive value towards the development of metastatic disease but not in relation to variations in aggressiveness or T staging inside the non-metastatic PC. Our results suggest an unlikely introduction of these analyses into clinical practice in support of validated PC risk predictors.

Compared Efficacy of Adjuvant Intravesical BCG-TICE vs. BCG-RIVM for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC): A Propensity Score Matched Analysis.

BACKGROUND: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. METHODS: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan-Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. RESULTS: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24-77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan-Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25-0.81). CONCLUSION: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

How to Predict Outcomes from a Biofeedback and Pelvic Floor Muscle Electric Stimulation Program in Patients with Urinary Incontinence after Radical Prostatectomy.

OBJECTIVES: The objective of this study was to analyze the pre-operative and intra-operative variables that can condition urinary incontinence (UI) after radical prostatectomy (RP), as well as continence rate recovery during a pelvic floor rehabilitation program. MATERIALS AND METHODS: A total of 72 cases with UI after RP were prospectively examined. All cases were homogeneously treated by the same surgeon, using the same RP technique. A combination of biofeedback (BF) and pelvic floor electric stimulation (PFES) performed by the same clinician and using the same protocol was used. Clinical, pathologic and surgical variables were analyzed in terms of 24 h pad test results (pad weight and pad-free status). RESULTS: Prostate volume (PV) strongly varied from 24 to 127 cc (mean ± SD 46.39 ± 18.65 cc), and the baseline pad weight varied from 10 to 1500 cc (mean ± SD 354.29 ± 404.15 cc). PV strongly and positively correlated with the baseline pad weight (r = 0.4215; p = 0.0269) and inversely with the three-month pad weight (r = - 0.4763; p = 0.0213) and pad-free status (r =- 0.3010; p = 0.0429). The risk of a residual pad weight >10 g after the rehabilitative program significantly increased according to PV (p = 0.001) and the baseline pad weight (p = 0.002 and < 0.0001). In particular, PV > 40 cc and a baseline pad weight >400 g significantly (p = 0.010 and p < 0.0001, respectively) and independently predicted a 5.7 and a 35.4 times increase in the risk of a residual pad weight at the three-month follow-up, respectively. CONCLUSION: This is the first prospective trial whose primary objective is to verify the possible predictors, such as PV, that are able to condition the response to a pelvic floor rehabilitation program for UI after RP.

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis.

INTRODUCTION: The aim of this article was to analyze whether operative time and blood loss during radical prostatectomy (RP) can significantly influence surgical margins (SM) status and post-operative functional outcomes. MATERIAL AND METHODS: We prospectively analyzed prostate cancer (PC) patients undergoing RP, using robot-assisted (RARP) or laparoscopic (LRP) procedures. Blood loss was defined using the variation in hemoglobin (Hb, g/dl) values from the day before surgery and no later than 4 hours after surgery. RESULTS: From a whole population of 413 cases considered for RP, 67% underwent LRP and 33.0% RARP. Positive SM (SM+) were found in 33.9% of cases. Mean surgical operative time was 172.3 ±76 min (range 49-485), whereas blood loss was 2.3 ±1.2 g/dl (range 0.3-7.6). Operative time and blood loss at RP were not significantly correlated (r = -0.028275; p = 0.684). SM+ rates significantly (p = 0.002) varied by operative time; a higher SM+ rate was found in cases with an operative time <120 min (41.2%) and >240 min (53.4%). The risk of SM+ significantly increased 1.70 and 1.94 times in cases with an operative time <120 min and >240 min, respectively, independently to the surgical approach. The rate of erectile disfunction (ED) varied from 22.4% to 60.3% between <120 min and >240 min procedures (p = 0.001). According to blood loss, SM+ rates slightly but significantly (p = 0.032) varied; a higher rate of SM+ was found in cases with a Hb variation between 2-4 g/dl (35.9%). CONCLUSIONS: Independently to the surgical approach, operative time, more than blood loss at RP, represents a significant variable able to influence SM status and post-operative ED.