A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation.

BACKGROUND: Premature ejaculation (PE) is a common male neurobiological sexual disorder, related to a disturbance in central serotonin (5-hydroxytryptamine or 5-HT) neurotransmission. AIM: To assess the efficacy of a single oral dose of 5HT1A receptor antagonist GSK958108 on ejaculation latency time (ELT) in male subjects suffering from PE. METHODS: A total of 35 male subjects were enrolled in a Phase 1 double-blind, placebo-controlled, parallel group masturbation-model study. All subjects completed the study. No subject was withdrawn from the study. There were no major protocol deviations reported during the study. OUTCOMES: The primary outcome of the study was to evaluate the effect of a single oral dose of 5HT1A receptor antagonist GSK958108 on ELT as measured in the masturbation model; additionally, we investigated drug's safety and tolerability. RESULTS: In the 3 mg GSK958108 treatment group, the ELT was estimated to be 16% longer (1.542 vs 1.328, 95% CI: -16% to +61%) than if the subjects had taken placebo. In the 7 mg GSK958108 treatment group, the ELT was estimated to be 77% longer (2.346 vs 1.328, 95% CI: +28% to +144%) than in the placebo group. The systemic exposure to GSK958108 increased with dosage between 3 mg and 7 mg. A significant trend toward an increase of ELT was observed with increasing plasma concentrations of GSK958108. A total of 4 patients all treated with 7 mg dose experienced minor drug related adverse events (5 adverse events in 4 patients): somnolence (n = 3), headache (n = 1), tinnitus (n = 1). CLINICAL IMPLICATIONS: In the current double-blind, placebo-controlled parallel group study the 5HT1A receptor antagonist GSK958108 was tested in 3 mg and 7 mg doses for PE treatment in humans. It was shown that GSK958108 significantly delayed ejaculation showing a new and safe alternative in PE treatment. STRENGTHS & LIMITATIONS: The present study showed innovative results suggesting an important role of 5HT1A receptor antagonist in the PE treatment. However, the use of masturbation model and the small population are the main limitations of this investigation. CONCLUSION: 5HT1A receptor antagonist GSK958108 3 mg per day and 7 mg per day was found to be well-tolerated, safe and effective for the treatment of PE subjects and demonstrated a strong association between 5HT1A receptors and ejaculation control in humans (NCT00861484). Migliorini F, Tafuri A, Bettica P, et al. A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation. J Sex Med 2021;18:63-71.

The Influence of Endogenous Testosterone on Incidental Prostate Cancer after Transurethral Prostate Resection.

OBJECTIVE: The aim of the study was to test the hypothesis that endogenous total testosterone (TT) may relate to incidental prostate cancer (iPCA) in patients with lower urinary tract symptoms (LUTS) associated with prostate enlargement undergoing transurethral resection of the prostate (TURP). METHODS: The hypothesis was tested in contemporary cohort of patients who underwent TURP because of LUTS due to prostate enlargement after excluding the suspect of PCA. In period running from January 2017 to November 2019, 389 subjects were evaluated. Endogenous testosterone was measured preoperatively between 8:00 and 10:00 o'clock in the morning. Relationships between TT and iPCA were evaluated by statistical methods. RESULTS: Overall, iPCA was detected in 18 cases (4.6%) with clinical stage cT1a or International Society of Urologic Pathology (ISUP) < 2 in 11 patients (61.1%). Endogenous testosterone was inversely associated with age and BMI in the study population but not in the subgroup with iPCA in wholly endogenous TT strongly correlated to both number of chips involved by cancer (Pearson's correlation coefficient, r = 0.553; p = 0.017) and ISUP > 2 (r = 0.504; p = 0.033). The positive association of endogenous TT with both tumor load and tumor grade was confirmed by the linear regression model with high-regression coefficients for the former (regression coefficient, b = 0.307; 95% confidence interval, 95% CI: 0.062-0.551; and p = 0.017) as for the latter (b = 5.898; 95% CI: 0.546-11.249; and p = 0.033). CONCLUSIONS: Preoperative endogenous TT is associated with features of iPCA. The influence of iPCA on endogenous testosterone needs to be addressed by a large multicenter prospective trial.

Prostate volume index and prostatic chronic inflammation predicted low tumor load in 945 patients at baseline prostate biopsy.

PURPOSE: To assess associations of prostate volume index (PVI), defined as the ratio of the volume of the central transition zone to the volume of the peripheral zone of the prostate and prostatic chronic inflammation (PCI) as predictors of tumor load by number of positive cores (PC) in patients undergoing baseline random biopsies. METHODS: Parameters evaluated included age, PSA, total prostate volume, PSA density, digital rectal exam, PVI, and PCI. All patients underwent standard transperineal random biopsies. Tumor load was evaluated as absent (no PC), limited (1-3 PC), and extensive (more than 3 PC). The association of factors with the risk of tumor load was evaluated by the multinomial logistic regression model. RESULTS: The study evaluated 945 patients. Cancer PC were detected in 477 (507%) cases of whom 207 (43.4%) had limited tumor load and 270 (56.6%) had extensive tumor load. Among other factors, comparing patients with limited tumor load with negative cases, PVI [odds ratio, OR = 0.521, 95% confidence interval (CI) 0.330-0.824; p < 0.005] and PCI (OR = 0.289, 95% CI 0.180-0.466; p < 0.0001) were inversely associated with the PCA risk. Comparing patients with extensive tumor load with negative patients, PVI (OR = 0.579, 95% CI 0.356-0.944; p = 0.028), and PCI (OR = 0.150, 95% CI 0.085-0.265; p < 0.0001), predicted PCA risk. Comparing extensive tumor load with limited tumor load patients, PVI and PCI did not show any association with the tumor load. CONCLUSIONS: Increased PVI and the presence of PCI decreased the risk of increased tumor load and associated with less aggressive prostate cancer biology in patients at baseline random biopsies.

Elevated prostate volume index and prostatic chronic inflammation reduce the number of positive cores at first prostate biopsy set: results in 945 consecutive patients.

OBJECTIVE: To assess the association between prostate volume index (PVI), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA). PVI is the ratio between the central transition zone volume (CTZV) and the peripheral zone volume (PZV). MATERIALS AND METHODS: Parameters evaluated included age, prostate specific antigen (PSA), total prostate volume (TPV), PSA density (PSAD), digital rectal exam (DRE), PVI, PCI and number of positive cores (NPC). All patients underwent baseline 14-core, trans-perineal random biopsies. Associations of parameters with the NPC were investigated by univariate and multivariate linear regression analysis. RESULTS: Between September 2010 to September 2017, 945 patients were evaluated. PCA was detected in 477 cases (50.7%), PCI in 205 cases (21.7%). PCA patients, compared to negative cases, were older (68.3 vs. 64.4 years) with smaller TPV (36 vs. 48.3mL) and CTZV (19.2 vs. 25.4), higher PSAD (0.24 vs. 0.15ng/mL/mL), further PVI values were lower (0.9 vs. 1.18) and biopsy cores less frequently involved by PCI (9.4% vs. 34.2%). High PVI and the presence of PCI were independent negative predictors of NPC in model I considering PSA and TVP (PVI, regression coefficient, RC -0,6; p=0.002) and PCI (RC -1,4; p<0.0001); and in model II considering PSAD (PVI:RC -0,7; p<0,0001; and PCI: RC -1,5; p<0.0001). CONCLUSIONS: High PVI and the presence of PCI lowered the mean rate of NPC and is associated with less aggressive tumor biology expressed by low tumor burden. PVI can give prognostic information before planning baseline random biopsies. Confirmatory studies are required.

Positive Association between Basal Total Testosterone Circulating Levels and Tumor Grade Groups at the Time of Diagnosis of Prostate Cancer.

INTRODUCTION: To test the hypothesis that basal total testosterone (TT) levels are associated with International Society of Urologic Pathology (ISUP) tumor grade groups at the time of diagnosis of prostate cancer (PCA). METHODS: From November 2014 to March 2018, preoperative TT and PSA were measured in 601 consecutive patients who were not under androgen deprivation and undergoing surgery for PCA. Patients were classified into low (ISUP 1; reference group), intermediate (ISUP 2/3), and high (ISUP 4/5) tumor grade groups. The association of TT and other clinical factors with tumor groups was evaluated by multinomial multivariate regression analysis. RESULTS: 218 patients (36.3%) were biopsy low grade (ISUP 1), 297 (49.4%) intermediate grade (ISUP 2/3), and 86 (14.3) high grade (ISUP 4/5). Median basal circulating TT levels progressively increased as tumor grade groups increased. On multivariate models, TT, among other clinical factors, was positively associated with the risk of intermediate (OR 1.001; p = 0.023) and high tumor grades (OR 1.002, p = 0.022) compared to low-grade cancers. CONCLUSIONS: Increased endogenous circulating basal TT levels were positively associated with ISUP tumor grade groups at the time of diagnosis indicating a close association with tumor biology. Basal TT levels may reflect the heterogeneity of the cancer population.

Lymph Nodes Invasion of Marcille's Fossa Associates with High Metastatic Load in Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection: The Role of "Marcillectomy".

INTRODUCTION: To assess the incidence of malignancy involvement of lymph nodes (LNs) in Marcille's fossa in patients undergoing robot assisted radical prostatectomy (RARP) and extended pelvic lymph nodes dissection (ePLND) for prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: Between January 2014 and December 2017, details of patients who underwent RARP and ePLND were prospectively analysed. All the nodal packets were dissected separately, grouped into left and right nodes and submitted in separate packages to dedicated pathologist. RESULTS AND LIMITATIONS: Two hundred and twenty-one patients underwent ePLND and RARP in the study period. In aggregate, Marcille's LNs involvement was found in 5 (2.3%) of patients, 2 on the left side and 3 on the right side. Per cent of positive cores and Gleason at biopsy are clinical predictors of LNs invasion; moreover, in the surgical specimen, seminal vesicle invasion and high-grade cancer were factors related to loco-regional metastases. CONCLUSIONS: Marcille's nodes involvement is associated to contemporarily multiple LN metastases in other template locations in high-risk PCa patients. The Marcille's lymphadenectomy would be recommended when planning an ePLND in high-risk PCa.

Prostate Volume Index Is Able to Differentiate between Prostatic Chronic Inflammation and Prostate Cancer in Patients with Normal Digital Rectal Examination and Prostate-Specific Antigen Values <10 ng/mL: Results of 564 Biopsy Naïve Cases.

INTRODUCTION: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume to the peripheral zone volume, and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) risk in patients presenting with normal digital rectal exam and prostate-specific antigen (PSA) ≤10 ng/mL at baseline random biopsies. METHODS: We evaluated patients with a negative digital rectal examination (DRE) and a PSA ≤10 ng/mL who underwent initial baseline prostate biopsy from 2010 to 2017. Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core trans-perineal standard biopsies. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing 2 multivariate models: model I included age, TPV, PVI and PCI; model II included age, PSAD, PVI and PC. RESULTS: Overall, 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases respectively. In patients with PCA, the median PVI was 0.83 (interquartile range [IQR] 0.62-1.04). In patients with PCI, the median PVI was 1.12 (IQR 0.81-1.47). In model I, age (OR 1.080) TPV (OR 0.961), PVI (OR 0.517) and PCI (OR 0.249) were associated with PCA risk. In model II, the age (OR 1.074), PSAD (OR 3.080), PVI (OR 0.361) and PCI (OR 0.221) were associated with PCA risk. CONCLUSIONS: Higher PVI and PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ≤10ng/mL at baseline random biopsy. In this subset of patients, PVI is able to differentiate patients with PCI or PCA.

Long-term follow-up of anterior vaginal repair: A comparison among colporrhaphy, colporrhaphy with reinforcement by xenograft, and mesh.

AIMS: To assess the long-term complications and outcomes in patients treated for pelvic organ prolapse (POP) with transvaginal anterior colporrhaphy (AC) alone, transvaginal naterior AC with reinforcement by using porcine Xenograft (AC-P) (Pelvisoft® Biomesh), and transvaginal anterior repair with polypropylene mesh (AC-M). METHODS: This was a retrospective analysis of 109/123 consecutive patients, who underwent cystocele repair: 42 AC, 19 AC-P, and 48 AC-M. Subjective outcomes included validated questionnaires as well as questions that had not been previously validated. Objective outcomes have been evaluated considering failure the anterior vaginal wall recurrence >2 stage POP-Quantification. Statistical analysis included the chi-square or Fisher exact test. RESULTS: The mean follow-up was 94.80 ± 51.72 months (19-192 months). In all groups, the patient's personal satisfaction was high. There was no evidence of difference in outcome based on whether a biological graft was or was not performed, or whether synthetic mesh was used to reinforce the repair. Data showed a higher rate of complications in the AC-M group (P < 0.05) that could explain the lower subjective satisfaction of these patients. CONCLUSIONS: This study evaluated long-term outcomes to anterior vaginal repair over a period of more than 5 years in all the groups. Our data show that anterior vaginal repair with mesh and xenograft did not improve significantly objective and subjective outcomes. Rather, prosthetic device use leads to higher rate of complications.

The preoperative serum ratio of total prostate specific antigen (PSA) to free testosterone (FT), PSA/FT index ratio, and prostate cancer. Results in 220 patients undergoing radical prostatectomy.

OBJECTIVES: To evaluate associations of preoperative total prostate specific antigen (PSA) to free testosterone (FT), the PSA/FT index ratio, with features of pathology prostate cancer (PCA) and to investigate its prognostic potential in clustering the PCA population. PATIENTS AND METHODS: After excluding criteria, the records of 220 patients who underwent radical prostatectomy (RP) were retrospectively reviewed. Serum samples of PSA, total testosterone (TT) and FT were collected at 8.00 A.M., one month after biopsies and before RP. The PSA/FT ratio was computed in the population of patients who were clustered in groups according to ranking intervals of the PSA/FT ratio which identified at least 4 clusters which were coded as A, B, C, and D. The independent associations of the PSA/FT index ratio were assessed by statistical methods and a two-sided P < 0.05 was considered to indicate statistical significance. RESULTS: TT correlated to FT which was a significant predictor of PSA in the population of patients who were subsequently clustered, according to increasing interval values of the PSA/FT index ratio, in groups that showed a stronger linear association of FT with PSA. The PSA/FT index ratio significantly associated with pathology features of prostate cancer such as pathology Gleason score (pGS), invasion of the seminal vesicles (pT3b), proportion of positive cores (P+) and proportion of cancer involving the volume of the prostate. In the population of patients, TT, PSA/FT index ratio and P+ independently associated with pGS ≥ 7 and pT3b; moreover, the odds ratio (OR) of the PSA/FT index ratio resulted 9.11 which was stronger than TT (OR = 1.11) and P+ (OR = 8.84). In the PCA population, TT, PSA/FT index ratio and P+ also independently associated with pT3b PCA; interestingly, the OR of PSA/FT index resulted 54.91 which was stronger than TT (OR = 1.31) and P+ (26.43). CONCLUSIONS: Preoperative PSA/FT index ratio is an independent strong factor which directly associates with aggressive features of pathology PCA; moreover, it might express prognostic potential for clustering the patient population in risk classes. Confirmatory studies are required.

Prostate volume index and chronic inflammation of the prostate type IV with respect to the risk of prostate cancer.

BACKGROUND: Benign prostatic hyperplasia and prostate cancer (PCA) alter the normal growth patterns of zonal anatomy with changes of prostate volume (PV). Chronic inflammatory infiltrates (CII) type IV are the most common non-cancer diagnosis of the prostate after biopsy. OBJECTIVE: To evaluate associations of both PV index (PVI), i.e. the ratio of transitional zone volume (TZV) to peripheral zone volume (PZV), and CII with PCA in patients undergoing biopsy. SUBJECTS AND METHODS: Between January 2007 and December 2008, 268 consecutive patients who underwent prostate biopsy were retrospectively evaluated. PV and TZV were measured by transrectal ultrasound. PZV was computed by subtracting the PV from the TZV. CII were evaluated according to standard criteria. Significant associations of PVI and the presence of CII (CII+) with PCA risk were assessed by statistical methods. RESULTS AND LIMITATIONS: We evaluated 251 patients after excluding cases with painful rectal examinations, prostate-specific antigen (PSA) >20 µg/ml and metastases. The PCA detection rate was 41.1%. PVI was a negative independent predictor of PCA. A PVI ≤1.0 was directly [odds ratio (OR) = 2.36] associated with PCA, which was detected more frequently in patients with a PVI ≤1.0 (29.1%) than in those with a PVI >1.0 (11.9%). CII+ was inversely (OR = 0.57) and independently associated with PCA, which was detected less frequently in cases with CII (9.9%) than in those without CII (21.1%). Potential study limitations might relate to the fact that PV was not measured by prostatectomy specimens and there was PSA confounding for CII and PCA. CONCLUSIONS: Low values of PVI are directly associated with risk of PCA, which was almost 2.5 times higher in patients with a PVI ≤1.0. The PVI might be an effective parameter for clustering patients at risk of PCA. CII+ was inversely associated with risk of PCA and decreased the probability of detecting PCA by 43%. The role of the PVI and CII in PCA carcinogenesis needs further research.

Associations of pretreatment serum total testosterone measurements with pathology-detected Gleason score cancer.

BACKGROUND AND OBJECTIVE: Prostate cancer is an endocrine-dependent tumor which is still under-investigated for physiopathology factors related to its natural history. The association of pretreatment total testosterone (TT) serum levels with prostate cancer is still a controversial topic. The objective of this study was to investigate potential associations and functional relationships of preoperative TT serum level and pathology-detected Gleason score (pGS). MATERIALS AND METHODS: Pretreatment and pathological variables of 220 patients operated with radical prostatectomy were retrospectively reviewed. Age, prostate-specific antigen (PSA), percentage of positive biopsy cores (P+), biopsy Gleason score (bGS), pGS, TT and free testosterone were the continuous variables, while clinical stage (cT: cT1c, cT2/3), biopsy Gleason pattern (bGP: ≤3+3, 3+4, >3+4), pathology Gleason pattern (pGP: ≤3+3, 3+4, >3+4), pathology stage (pT: pT2, pT3a, pT3b), pathology nodal staging (pN: pN0, pN1, pNx) and surgical margin invasion by cancer (R-, R+) were the categorical variables. Statistical methods were computed for assessing associations of TT and pGS; moreover, simple and multiple linear regression analysis (SLRA and MLRA) were used for assessing functional relationships of TT and pGS. RESULTS: High-grade tumors (pGS ≥8.0) were associated with bGS >6.0 (p < 0.0001), pGP ≥3+4 (p < 0.0001), P+ >0.31% (p = 0.006), cT2/3 (p = 0.01), TT >15.5 nmol/l (p = 0.0004) and, to a lesser extent, PSA >6.27 µg/l (p = 0.06). The odds ratio (OR) ranked as follows: 2.01 (PSA >6.27 µg/l), 2.88 (cT2/3), 3.23 (P+ >0.31%), 5.53 (TT >15.5 nmol/l) and 12.09 (pGP ≥3+4 and pGS ≥8.0). On SLRA, pGS variation was significantly predicted by bGS (p < 0.0001), P+ (p < 0.0001), PSA (p = 0.0005) and TT (p = 0.02); on MLRA, pGS variation was still significantly predicted by bGS (p < 0.0001), P+ (p = 0.04), PSA (p = 0.03) and TT (p = 0.002). When bGS, P+, PSA and TT were dichotomized to their median value, only bGS (p < 0.0001) and TT (p = 0.001) showed independence in predicting pGS variation. The best model for predicting pGS variations was by dichotomizing TT above its median (>15.5 nmol/l) because the predictive coefficient increased to 0.32, which means that patients with TT >15.5 have a significantly higher estimated risk for high-grade pGS than patients with TT ≤15.5 nmol/l (OR = 1.31). CONCLUSION: In a patient population undergoing radical prostatectomy, increased pretreatment serum measurements of TT are associated with and functionally related to high-grade pGS; moreover, baseline TT together with bGS and PSA are important factors for predicting pGS and assessing high-grade tumors. Baseline TT serum levels might have prognostic potential for assessing treatment response for continuous as well as intermittent androgen deprivation therapy.

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer.

BACKGROUND: Chronic inflammatory infiltrate (CII) might be involved in prostate cancer (PCA) and benign hyperplasia (BPH); however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. OBJECTIVE: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. DESIGN, SETTING, AND PARTICIPANTS: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years) and PSA (ug/l); moreover, CII+, glandular atrophy (GA+), glandular hyperplasia (GH+), prostate Intraepithelial neoplasm (PIN+), atypical small acinar cell proliferation (ASAP+) and PCA positive cores (P+) were evaluated as categorical and continuous (proportion of positive cores). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of CII+ and PCA risk were assessed by statistical methods. RESULTS AND LIMITATIONS: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8) resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26) and HGPCA (P = 0.0005; OR = 0.05). Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. CONCLUSIONS: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in PCA carcinogenesis remains controversial and needs further research.

Single-layer versus double-layer renorrhaphy technique during robot-assisted partial nephrectomy: impact on perioperative outcomes, complications, and functional outcomes.

BACKGROUND: The debate between single-layer and double-layer renorrhaphy techniques during robot-assisted partial nephrectomy (RPN) represents a subject of ongoing discourse. The present analysis aims to compare the perioperative and functional outcomes of single- versus double-layer renorrhaphy during RPN. METHODS: Study data were retrieved from prospectively maintained institutional database (Jan2018-May2023). Study population was divided into two groups according to the number of layers (single vs. double) used for renorrhaphy. Baseline and perioperative data were compared. Postoperative surgical outcomes included type and grade of complications as classified according to Clavien-Dindo. Serum creatinine and estimated glomerular filtration rate were used to measure renal function. RESULTS: Three hundred seventeen patients were included in the analysis: 209 received single-layer closure, while 108 underwent double-layer renorrhaphy. Baseline characteristics were not statistically different between the groups. Comparable low incidence of intraoperative complications was observed between the cohorts (P=0.5). No difference was found in terms of mean (95% CI) Hb level drop postoperation (single-layer: 1.6 g/dL [1.5-1.7] vs. double-layer: 1.4 g/dL [1.2-1.5], P=0.3). Overall and "major" rate of complications were 16% and 3%, respectively, with no difference observed in terms of any grade (P=0.2) and major complications (P=0.7). Postoperative renal function was not statistically different between the treatment modalities. At logistic regression analyses, no difference in terms of probability of overall (OR 0.82 [0.63-1.88]) and major (OR 0.94 [0.77-6.44]) complications for the number of suture layers was observed. CONCLUSIONS: Single-layer and double-layer renorrhaphy demonstrated comparable perioperative and functional outcomes within the setting of the present study.

Outcomes of da Vinci® versus Hugo RAS® radical prostatectomy: focus on postoperative course, pathological findings, and patients' health-related quality of life after 100 consecutive cases (the COMPAR-P prospective trial).

BACKGROUND: This study aims to prospectively compare the outcomes of robot-assisted radical prostatectomy (RARP) performed using the Hugo RAS and da Vinci Xi systems, focusing on the postoperative course, pathological findings, and health-related quality of life. METHODS: The COMPAR-P trial, a prospective post-market study (clinical-trials.org NCT05766163), commenced in March 2023, enrolling patients for RARP performed with either da Vinci or Hugo RAS without selection criteria for up to 50 consecutive cases per system. Two experienced console surgeons performed the procedures according to a standardized technique. The study evaluated differences between da Vinci and Hugo RAS regarding the postoperative course, pathology findings, 30-day PSA value, functional metrics, and health-related quality of life using SF-36 and University of California Los Angeles Prostate Cancer Index questionnaires. RESULTS: Fifty patients underwent DV-RARP and H-RARP each. Postoperative complications, pathological data, and quality of life metrics did not significantly differ between the groups. Noteworthy limitations include the comparison between the first 50 H-RARP and last 50 DV-RARP cases, as well as the potential influence of surgeons' specialized expertise on the generalizability of findings. CONCLUSIONS: This prospective study of 100 unselected patients undergoing RARP with either da Vinci or Hugo RAS systems reveals comparable outcomes in postoperative course, pathology, functional metrics, and health-related quality of life. However, further research with larger sample sizes, longer follow-up periods, and diverse surgical expertise is essential to validate these findings and better understand the implications for clinical practice.

High-volume surgeons decrease operating time in robot-assisted radical prostatectomy: results in 1229 patients.

BACKGROUND: The aim is to evaluate factors impacting operating time (OT) during robot-assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND) for prostate cancer. METHODS: Overall, 1289 patients underwent RARP from January 2013 to December 2021. ePLND was performed in 825 cases. Factors potentially associated with OT variations were assessed. Three low-volume (LVS) and two high-volume surgeons (HVS) performed the procedures. A linear regression model was computed to assess associations with OT variations. RESULTS: When RARP was performed by HVS an OT decrease was observed independently by significant clinical (Body Mass Index [BMI]; prostate volume [PV]) and anatomical/perioperative features (prostate weight [PW]; intraoperative blood loss [BL]) both in clinical (change in OT: -42.979 minutes; 95% CI: -51.789; -34.169; P<0.0001) and anatomical/perioperative models (change in OT: -40.020 minutes; 95% CI: -48.494; -31.587; P<0.0001). A decreased OT was observed in clinical (change in OT: -27.656 minutes; 95% CI: -33.449; -21.864; P<0.0001) and anatomical/perioperative (change in OT: -24.935 minutes; 95% CI: -30.562; -19.308; P<0.0001) models also in case of RARP with ePLND performed by HVS, independently by BMI, PV, PSA as well as for PW, seminal vesicle invasion, positive surgical margins, and BL. CONCLUSIONS: In a tertiary academic referral center, OT decreased when RARP was performed by HVS, independently of adverse clinical and anatomical/perioperative factors. Available OT loads can be planned to optimize waiting lists, teaching tasks, operative costs, and surgeon's volume.

Accuracy of preoperative endo-rectal coil magnetic resonance imaging in detecting clinical under-staging of localized prostate cancer.

OBJECTIVES: To assess the accuracy of intra-rectal coil magnetic resonance imaging (ER-MRI) for staging early prostate cancer (EPC). MATERIALS AND METHODS: ER-MRI was performed with the Magnetom Symphony 1.5 Tesla system. ER-MRI and pathology findings were statistically correlated. RESULTS: One hundred and fifty-four consecutive patients underwent radical prostatectomy (RRP) for EPC (cT1c-2 Nx M0). An average age was 66, mean PSA 11.04 µg/L (median 7.33 µg/L) and mean pathologic Gleason score 6. Pathology detected 97 out of 154 patients (63 %) as EPC and 57 cases (37 %) as extra-prostate extension (EPED) (pT3) with extra-capsular extension (ECE) (pT3a) in 41 (27 %) and seminal vesicle invasion (SVI) (pT3b) in 16 (10 %). ER-MRI staged 100 patients (65 %) as cT2 and 54 (35 %) as EPED with ECE in 37 cases (24 %) and SVI in 17 (11 %). ER-MRI sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy resulted respectively 0.78, 0.96, 0.86, 0.92, 0.91 for ECE as well as 0.88, 0.98, 0.82, 0.99 and 0.97 for SVI. CONCLUSION: ER-MRI was effective in detecting preoperative EPC under-staging. In the next future, multi-parametric 3-Tesla ER-MRI will be the procedure for diagnosing, staging and following-up prostate cancer patients.

Serum total testosterone is a significant preoperative variable independently contributing to separating the prostate cancer population into prostatectomy Gleason score groups.

AIM: To investigate the potential of preoperative serum total testosterone (TT) in contributing to the definition of separate prostatectomy Gleason score (pGS) groups of the prostate cancer (PCa) population. MATERIALS AND METHODS: The data of 220 patients operated on for PCa were retrospectively reviewed. No patient had previously received 5α-reductase inhibitor, luteinizing hormone-releasing analogs or testosterone replacement treatment. The patient population was grouped according to the pGS as 6 = 3+3, 7 = 3+4, 7 = 4+3 and 8-10. Eight variables were simultaneously investigated in each group: prostate-specific antigen (PSA), TT, free testosterone, age, percentage of positive prostate biopsy cores (P+), biopsy Gleason score (bGS), overall cancer volume estimated as percentage of prostate volume (V+) and prostate weight (Wi). Univariate analysis of variance (ANOVA), multivariate analysis of variance (MANOVA) and multivariate discriminant analysis (MDA) were the statistical methods used for evaluating the data. RESULTS: There were 89 patients in pGS 6 = 3+3, 84 in pGS 7 = 3+4, 24 in pGS 7 = 4+3 and 23 in pGS 8-10. ANOVA showed that bGS (p < 0.0001), P+ (p < 0.0001), V+ (p < 0.0001), PSA (p = 0.0001), Wi (p = 0.0002) and TT (p = 0.01) were significantly different in the four pGS groups. MANOVA tests showed that only bGS (p < 0.0001), V+ (p = 0.0003), TT (p = 0.001) and, to a lesser extent, PSA (p = 0.06) were the significant variables that individually and independently contributed a significant amount to separation of the four pGS groups of the PCa population. MDA showed that the independent variables ranked as bGS (p < 0.0001), TT (p = 0.001), V+ (p = 0.001) and PSA (p = 0.06). CONCLUSIONS: Serum TT is a significant preoperative variable that independently contributes to separating the PCa population into pGS score groups. Pretreatment baseline serum TT levels should be measured and their inclusion in neural networks predicting PCa natural history be considered in the patient population diagnosed with PCa.

Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer and subsequent cluster selection of the patient population undergoing standard radical prostatectomy.

AIM: A preceding exploratory analysis has shown that follicle-stimulating hormone (FSH) was significantly correlated to and predicted by prostate-specific antigen (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of initial diagnosis of prostate cancer in an operated population clustered according to the FSH/PSA ratio. PATIENTS AND METHODS: The study included 93 patients who underwent standard radical prostatectomy. Age, percentages of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH, prolactin hormone (PRL), total testosterone (TT), free testosterone (FT), estradiol (ESR) and PSA were the continuous variables. Category variables were pT and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was clustered according to the FSH/PSA ratio which was computed from empirical data and then ranked for clustering the population as groups A (range 0.13 ≤ FSH/PSA ≤ 0.20), B (range 0.20 < FSH/PSA ≤ 0.50), C (range 0.50 < FSH/PSA ≤ 0.75), D (range 0.75 < FSH/PSA ≤ 1.00), E (range 1.00 < FSH/PSA ≤ 1.25), F (range 1.25 < FSH/PSA ≤ 2.00), G (range 2.00 < FSH/PSA ≤ 2.25), H (range 2.25 < FSH/PSA ≤ 6.40) and I (range 6.40 < FSH/ PSA ≤ 19.40). The model was assessed by simple linear regression analysis and differences between the groups were investigated by analysis of variance (ANOVA) for continuous variables and by contingency tables for category variables. RESULTS: FSH was significantly correlated to and predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p < 0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p = 0.001). Also, clusters (A-I) differed significantly for mean values of FSH (p < 0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed significant different frequency distributions of pGPI (p = 0.02), pGPII (p = 0.0002) and bGPI (p = 0.04). CONCLUSION: The ranking FSH/PSA ratio significantly clustered, along the PTP axis, an operated population diagnosed with prostate cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters expressing different levels of hormonal disorder along the PTP axis and prognostic potential with different risks of progression. As a theory, in the current advancing world, the ranking FSH/PSA model might be considered as an interesting and effective tool for prostate cancer study as well as individualized, risk-adapted approaches of the disease. However, confirmatory studies are needed.