Renal Function Preservation in Purely Off-Clamp Sutureless Robotic Partial Nephrectomy: Initial Experience and Technique.

The aim of our study is to evaluate the effectiveness and safety of a sutureless off-clamp robot-assisted partial nephrectomy (sl-oc RAPN), particularly its impact on renal function. A multicenter study was conducted from April 2021 to June 2022. Patients diagnosed with a renal mass of >2 cm and a PADUA score of ≤6 consecutively underwent an sl-oc RAPN procedure. Tumor features, patients characteristics, and intraoperative outcomes were assessed. An evaluation of renal function was performed preoperatively, and again at 1 and 3 months after surgery by measuring the creatinine and blood urea nitrogen levels. The renal function of the two separate kidneys was assessed by a sequential renal scintigraphy performed before and at least 30 days after surgery. A total of 21 patients underwent an sl-oc RAPN. The median age was 64 years (IQR 52/70), the median tumor diameter was 40 mm (IQR 29/45), and the median PADUA score was 4 (3.5/5). The intraoperative outcomes included operative time (OT), 90 (IQR 74/100) min; estimated blood loss (EBL), 150 (IQR 50/300) mL; and perioperative complications, CD > 3 1(5%); only two patients presented positive surgical margins in their final histology (2/21, 10%). Compared to the preoperative value, a decrease in renal function was highlighted with a statistically significant median decrease of 10 mL/min (p < 0.01). The renal scintigraphy showed an overall decrease in renal function compared to the preoperative value, with a range in the operated kidney that varied from 0 to 15 mL/s and from 0% to 40%, with a median value of 4 mL/s and 12%. sl-oc RAPN is a safe procedure, with a minimal impact on kidney function alteration. This technique has proven effective in preserving renal function and maintaining optimal oncological outcomes with limited complications.

Sexual and reproductive health: level of knowledge and source of information in adolescence.

BACKGROUND: To date, there is a lack of a structured national plan of sexual education in Italy, with large interregional differences and poor uniformity in the promotion and learning of sexual health. AIM: The aim of this study was to evaluate the level of knowledge on sexuality and reproductive function among adolescents before and after a sexual education program, considering gender differences in the results. METHODS: A longitudinal and interventional study was conducted on high school students. Six sessions for each class were carried out by a multidisciplinary team. Anonymous questionnaires were administered to investigate basic knowledge of human sexuality and reproduction before and after intervention. OUTCOMES: Participants were high school students who completed the questionnaires. Outcomes included pre and posttest answers on the knowledge questionnaire in study population. RESULTS: We obtained data from 842 high school students (mean ± SD age, 16.11 ± 1.74 years). The main informative sources on sexuality were social media in 37.9% of participants; family, school, and scientific material were the main source in 15.1%, 5.2%, and 4.4%, respectively. A total score of 12.6 ± 3.4 (range, 1-20) was obtained on the knowledge questionnaire; specifically, the score was higher in females than males (12.8 ± 3.4 vs 11.9 ± 3.4, P = .0001). In males and females, a statistically significant increase in level of knowledge was found after the multidisciplinary intervention (14.5 ± 3.6, P = .0001). CLINICAL IMPLICATIONS: The lack of sexual education programs in schools in Italy compels adolescents to refer to frequently unreliable sources, such as social media and peers, contributing to misinformation and adoption of risky sexual behaviors. STRENGTHS AND LIMITATIONS: This study is based on a large sample size and highlights the importance of sexual education programs. The main limitations are a greater representation of the female population and the inclusive nature of the school (ie, an artistic school), attracting students who identify with sexual minorities. CONCLUSIONS: Adolescents have limited knowledge about sexuality and reproduction, with a notable gender disparity; sexual education programs in schools, providing information from sexuality experts, led to a substantial increase in knowledge and a reduction in the gender gap.

Purely Off-Clamp Sutureless Robotic Partial Nephrectomy for Novice Robotic Surgeons: A Multi-Institutional Propensity Score-Matched Analysis.

Objectives: To compare perioperative outcomes of patients treated with sutureless off-clamp robotic partial nephrectomy (sl-oc RAPN) by either a novice or an expert robotic surgeon at two different institutions. Methods: Data concerning two continuous series of patients with cT1-2N0M0 renal tumors treated with sl-oc RAPN either by a novice or an expert surgeon were extracted from prospectively populated institutional databases over the last 4 years. Perioperative outcomes as well as the baseline characteristics of patients and tumors were compared by using χ2 and Mann-Whitney tests for categorical and continuous variables, respectively. A 1:1 propensity match score analysis (PMSa) generated two homogeneous cohorts. Logistic regression analysis was performed to assess predictors of trifecta outcomes, defined as negative surgical margins, no Clavien-Dindo ≧ 3 grade complications, and no ≧ 30% postoperative eGFR reduction. Results: Overall, 328 patients were treated by an expert surgeon, while 40 were treated by a novice surgeon. After PMSa analysis, two cohorts of 23 patients each were generated, homogeneous for all baseline variables (p ≥ 0.07). Hospital stay was the only significantly different outcome observed between the two groups (5 days vs. 2 days; p < 0.001). No statistically significant differences were recorded when comparing trifecta outcomes (expert: 100% vs. novice: 87%; p = 0.07). In the logistic regression analysis, no statistically significant predictors of trifecta outcomes were recorded. Conclusions: sl-oc RAPN is a feasible and safe nephron sparing technique, even when performed by a novice robotic surgeon.

No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial.

BACKGROUND: The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. METHODS: Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. RESULTS: Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). CONCLUSIONS: This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.

Ejaculation sparing of classic and minimally invasive surgical treatments of LUTS/BPH.

BACKGROUND: The surgical landscape for Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH) has evolved with the introduction of Minimally Invasive Surgical Therapies (MISTs), recognizing the impact of sexual function on patients' well-being, and prioritizing ejaculation-sparing approaches. METHODS: This systematic review explored ejaculation sparing after classic endoscopic procedures and MISTs (iTind, Rezum, Urolift, Aquablation, and TPLA) and a literature search yielded 41 studies. RESULTS: While all procedures demonstrated efficacy in improving LUTS/BPH symptoms (IPSS, QoL, Qmax), a subset of studies evaluated ejaculatory function. Positive outcomes were noted, challenging the historical association of BPH surgeries with ejaculatory dysfunction. Variations in study design, patient cohorts, and limited long-term data present challenges. Notably, the lack of baseline specificity, use of alpha-blockers, and non-specific sexual function assessments underscore potential biases. CONCLUSIONS: Despite limitations, the review tentatively concluded that MISTs, including iTind, Rezum, Urolift, Aquablation, and TPLA, appear comparable in sparing ejaculation. Long-term studies are essential to validate sustainability, and comparative research should assess trade-offs between MISTs and traditional surgeries. Incorporating patient-reported outcomes and quality of life assessments will enhance future investigations, refining MISTs as standard therapeutic options for LUTS/BPH.

Post-Voided Residual Ratio Does Not Predict Trifecta Outcome after Transurethral Resection of Prostate.

The purpose of this study was to assess the importance of the post-void residual (PVR) ratio (PVR ratio) in achieving a favorable trifecta outcome for patients suffering from lower urinary tract symptoms and benign prostatic enlargement (LUTS-BPE) who undergo transurethral resection of the prostate (TURP). Starting from 2015, a series of patients with LUTS-BPE who underwent TURP were included in a forward-looking study. These patients were assessed using the international prostate symptom score (IPSS) screening tool, uroflowmetry, and a transrectal ultrasound to measure prostate volume (TRUS). Both the PVR urine volume and the PVR ratio (PVR-R), which is the PVR as a percentage of total bladder volume (voided volume + PVR), were measured. The assessment of outcomes was based on the trifecta favorable outcome, defined as meeting all of the following criteria: (1) absence of perioperative complications, (2) a postoperative IPSS of less than eight, and (3) a postoperative maximum urinary flow rate (Qmax) greater than 15 mL/s. A total of 143 patients were included, with a median age of 70 years (interquartile range 65-73). Of these, 58% (83/143) achieved a positive trifecta outcome. Upon conducting a multivariate analysis, both IPSS and Qmax were identified as predictors of a positive trifecta outcome, whereas the PVR-R did not prove to be an independent predictor. In summary, it was found that preoperative IPSS and Qmax are indicative of a trifecta outcome following TURP, whereas PVR-R is not.

Nocturia in Menopausal Women: The Link Between Two Common Problems of the Middle Age.

INTRODUCTION AND HYPOTHESIS: The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors, treatment needs and options for nocturia in peri-menopausal women. METHODS: This opinion article is a narrative review based on the expertise and consensus of a variety of key opinion leaders, in combination with an extensive literature review. This literature search included a thorough analysis of potential publications on both the PubMed Database and the Web of Science and was conducted between November 2022 and December 2022. The following key words were used "nocturia" and "menopause" or "nocturnal frequency and menopause." Moreover, key words including "incidence," "prevalence," "insomnia," "estrogen therapy," "metabolic syndrome," and "hot flushes" were used in combination with the aforementioned key words. Last, the reference lists of articles obtained were screened for other relevant literature. RESULTS: The perimenopause can be a trigger for inducing nocturia. Typically, obesity, body mass index (BMI), and waist circumference are risk factors for developing peri-menopausal nocturia. Presumably the development of peri-menopausal nocturia is multifactorial, with interplay among bladder, sleep, and kidney problems due to estrogen depletion after the menopause. First, impaired stimulation of estrogen receptors in the urogenital region leads to vaginal atrophy and reduced bladder capacity. Moreover, menopause is associated with an increased incidence of overactive bladder syndrome. Second, estrogen deficiency can induce salt and water diuresis through blunted circadian rhythms for the secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone system. Additionally, an increased incidence of sleep disorders, including vasomotor symptoms and obstructive sleep apnea signs, is observed. Oral dryness and a consequent higher fluid intake are common peri-menopausal symptoms. Higher insulin resistance and a higher risk of cardiovascular diseases may provoke nocturia. Given the impact of nocturia on general health and quality of life, bothersome nocturia should be treated. Initially, behavioral therapy should be advised. If these modifications are inadequate, specific treatment should be proposed. Systemic hormone replacement is found to have a beneficial effect on nocturia, without influencing sodium and water clearance in patients with nocturnal polyuria. It is presumed that the improvement in nocturia from hormonal treatment is due to an improvement in sleep disorders.

Major adverse cardiovascular events related to phosphodiesterase 5 inhibitors: analysis of real-life data from Eudra-Vigilance database.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the standard medical treatment for erectile dysfunction. Aim of our study was to evaluate the rate of major adverse cardiovascular events (MACE) reported during PDE5i treatment based on Eudra-Vigilance (EV) reports. METHODS: EV database is the system for managing and analyzing data on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area. MACE are defined as non-fatal stroke, non-fatal myocardial infarction, non-fatal congestive heart failure, revascularization after aorto-coronary graft bypass and cardiovascular death. We recorded the number of MACE for sildenafil, tadalafil, vardenafil, avanafil per category and severity until 1st July 2023. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall, 951 MACE events were reported. Most of them were observed in younger patients <65 years old (452/951 events, 48%). Overall, 377/8939 (4%) MACE events were observed for sildenafil, 221/5213 (4%) for tadalafil, 50/1029 (4%) for vardenafil and no events for avanafil. No significative differences were reported comparing sildenafil and tadalafil (PRR 0.71-0.99, IQR 0.61-1.35, P>0.05), neither sildenafil vs. vardenafil (PRR 0.68-0.79, IQR 0.43-1.55, P>0.05), neither tadalafil vs. vardenafil (PRR 0.77-0.95, IQR 0.64-1.30. P>0.05) even when compared for age. Comparison between different classes of age showed MACE were more frequent in patients younger than 65 years old taking sildenafil and tadalafil when compared to patients older than 85 years old (PRR 0.02-0.11. IQR 0.01-0.40. P<0.01) and when compared to patients in 65-85 class of age (PRR 0.02-0.12, IQR 0.01-0.95, P<0.01). CONCLUSIONS: Real life data is consistent with MACE related to PDE5i. PDE5is are infrequently (<5%) associated with MACE. However, risk seems higher in younger patients, particularly for sildenafil (452/951 events, 48%). Clinicians should consider these data when prescribing PDE5i especially in young patients.

Medications Mostly Associated With Ejaculatory Disorders: Assessment of the Eudra-Vigilance and Food and Drug Administration Pharmacovigilance Databases Entries.

OBJECTIVE: To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis. METHODS: The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) and the Eudra-Vigilance (EV) database were queried to identify medications more commonly associated to ejaculatory disorders from September 10, 2012 to June 1, 2023. Proportional Reported Ratios (PRRs) were computed for all the selected drugs. RESULTS: Overall, 7404 reports of ejaculatory disorders reports were identified, and of these, 6854 cases (92.6%) were attributed to ten specific medications. On FDA-FAERS and EV databases, Paroxetine and Tamsulosin were the main responsible of delayed ejaculation (103/448 events, 23.0%) and retrograde ejaculation (366/1033 events, 35.4%), respectively. Finasteride was mostly related to painful ejaculation and ejaculation failure, with 150 events (7.8%) and 735 events (38.4%) respectively. Within the group of high-risk medications, Sildenafil presented higher risk of ejaculatory disorders than Tadalafil (PRR=5.85 (95%CI 5.09-6.78), P < .01). CONCLUSION: Ten drugs were recognized to display significant reporting levels of ejaculatory disorders. Among them, Finasteride and Sildenafil were responsible for the most reports in FDA-FAERS and in EV databases, respectively. Physicians should thoroughly counsel patients treated with these drugs about the risk of ejaculatory disorders. Further integration into clinical trials is needed to enhance the applicability and significance of these results.

Residents and Consultants Have Equal Outcomes When Performing Transrectal Fusion Biopsies: A Randomized Clinical Trial.

The aim of our study was to compare the performance of residents vs. consultants in transrectal fusion prostate biopsies (FUS-PBs), as well as patient-reported comfort. Between January 2021 and October 2022, a consecutive series of patients undergoing FUS-PBs were randomized into two groups: (A) FUS-PBs performed by a consultant; (B) FUS-PBs performed by trained residents (>50 procedures). All patients underwent FUS-PBs with 12 systematic cores and 3/6 target cores. The detection rate and number of positive cores in the target lesion were compared between groups, and the patient's discomfort after the procedure was evaluated using the VAS scale. Overall, 140 patients with a median age of 72 years were enrolled. Overall, 69/140 (49.3%) presented prostate cancer and 53/69 (76.8%) presented a clinically significant cancer (Grade Group ≥ 2). Consultants presented a detection rate of 37/70 (52.9%) and residents a detection rate of 32/70 (45.7%) (p > 0.2); the mean number of positive cores in the index lesion was similar in both groups (1.5 vs. 1.1; p > 0.10). In terms of the patients' experiences, the procedure was well tolerated, with a median VAS score of 2 in both groups, with no statistically significant differences. Residents showed satisfactory outcomes in terms of detection rate, procedural time, and patient comfort when performing prostate biopsies. Residents, after adequate training, can safely perform prostate biopsies.

Quality of information and appropriateness of Open AI outputs for prostate cancer.

Chat-GPT, a natural language processing (NLP) tool created by Open-AI, can potentially be used as a quick source for obtaining information related to prostate cancer. This study aims to analyze the quality and appropriateness of Chat-GPT's responses to inquiries related to prostate cancer compared to those of the European Urology Association's (EAU) 2023 prostate cancer guidelines. Overall, 195 questions were prepared according to the recommendations gathered in the prostate cancer section of the EAU 2023 Guideline. All questions were systematically presented to Chat-GPT's August 3 Version, and two expert urologists independently assessed and assigned scores ranging from 1 to 4 to each response (1: completely correct, 2: correct but inadequate, 3: a mix of correct and misleading information, and 4: completely incorrect). Sub-analysis per chapter and per grade of recommendation were performed. Overall, 195 recommendations were evaluated. Overall, 50/195 (26%) were completely correct, 51/195 (26%) correct but inadequate, 47/195 (24%) a mix of correct and misleading and 47/195 (24%) incorrect. When looking at different chapters Open AI was particularly accurate in answering questions on follow-up and QoL. Worst performance was recorded for the diagnosis and treatment chapters with respectively 19% and 30% of the answers completely incorrect. When looking at the strength of recommendation, no differences in terms of accuracy were recorded when comparing weak and strong recommendations (p > 0,05). Chat-GPT has a poor accuracy when answering questions on the PCa EAU guidelines recommendations. Future studies should assess its performance after adequate training.

Statins may increase the risk of being diagnosed with prostate cancer.

BACKGROUND: Although statins are known to protect against cardiovascular accidents, their anti-inflammatory features could play a role in preventing tumorigenesis. We investigated the association between statin intake and prostate cancer (PCa) diagnosis and aggressiveness. METHODS: A retrospective analysis was performed. Our dataset on patients undergone systematic prostate biopsy from December 2008 to December 2022 was searched for histopathologic and clinical data. Prognostic Grade Group ≥3 tumors were defined as high-grade (HG). The association between Metabolic Syndrome (MetS), statin use and PCa diagnosis and HG disease was assessed using logistic regression analyses. RESULTS: Data on 1685 patients were collected; MetS affected 344 (20.4%) men and 138 (36.5%) were taking statins at least for 6 months at the time of biopsy. Among the 671 (39.8%) men diagnosed with PCa, 327 (48.7%) presented with a HG disease. Tumor incidence was higher among men taking statins, compared to controls (46.8% vs. 37.8%; P=0.002); also, high grade diseases were more common in the former group, but the difference did not reach statistical significance (49.1% vs. 48.6%; P=0.89). Statin intake (OR 1.44; 95% CI [1.05-1.98]; P=0.02) independently predicted PCa diagnosis but not high-grade disease (P=0.8). CONCLUSIONS: Statin use may be associated with an increased risk of PCa diagnosis.

Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries.

BACKGROUND: Drugs may have a direct causative role in triggering hematuria. The range of medications which may be responsible for hematuria is wide, but little is known on those which are most frequently involved. The aim of our study was to identify and compare drugs mostly related with hematuria. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the EudraVigilance (EV) database were queried to identify the drugs which were associated the most with hematuria individual reports till 30 September 2021. Rivaroxaban, aspirin, warfarin sodium, clopidogrel bisulfate, dabigatran etexilate mesylate, apixaban, warfarin, cyclophosphamide, lansoprazole, enoxaparin sodium, and ibuprofen were analyzed. Analysis per gender, age and severity was performed. Disproportional analysis was performed to compare drugs. RESULTS: Overall, 15,687 reports of hematuria were recorded in the FDA database and 15 007 in the EV database. Rivaroxaban and Warfarin appear to be the most dangerous medications in terms of hematuria when compared to the other medications (PRR>1, P<0.05) while apixaban is the safest one (PRR<1, P<0.05) when compared to the other medications. In terms of severity only 162/15 007 (1.08%) were fatal. Between the drugs analyzed cyclophosphamide 7.2%, enoxaparin (3%) and dabigatran (2.5%) presented a higher number of fatal hematuria episodes when compared to the other drugs (<1%). CONCLUSIONS: Anticoagulants and antiplatelets are more frequently related to hematuria episodes however some differences exist between them. Particularly warfarin and rivaroxaban should be prescribed with caution in patients at increased risk of hematuria. Prescribers should inform those treated with these medications about the risk of hematuria and its sequelae.

Prostate Cancer in Transgender Women: Epidemiology, Clinical Characteristics, and Management Challenges.

PURPOSE OF REVIEW: To systematically review the evidence on prostate cancer (PCa) in transgender women (TGW). RECENT FINDINGS: A total of 25 studies were included. Fourteen articles were case reports or case series describing 21 TGW with PCa; 11 papers focused primarily on assessing the incidence or screening of PCa in TGW. The median (range) age of patients with PCa was 63 (45-78) years. Median (range) PSA at diagnosis was 7.5 (0.4-1710) ng/mL. Prostate biopsy detected ISUP 3-5 in 10 (67%) cases. T3-4 stages were described in 7 (64%) patients. Three (14.3%) cases of nodal involvement and 2 (9.5%) of metastases were reported at diagnosis. First-line therapy included radical prostatectomy or radiotherapy ± androgen deprivation therapy in 14 (74 %) subjects. Median (range) follow-up was 24 (2-120) months. A good response to first-line therapy was recorded in 8 (47.1%) cases. Median (range) incidence of PCa in TGW was 44.1 (4.34-140) cases per 100,000 person-years. PCa was significantly less frequent in TGW than in cisgender males (HR 0.4, 95% CI 0.2-0.9). Risk of death after PCa diagnosis was significantly higher in TGW compared to cisgender males (HR 1.91, 95% CI 1.06-3.45). TGW had lower lifetime PSA rates (48% vs. 64.6%, p = 0.048) than cisgender males. Few cases of PCa in TGW are currently reported. PCa seems significantly less frequent in TGW than in cisgender males; however, some data suggest a possible higher mortality in this cohort. TGW appear to have less access to PSA testing than cisgender men.

Oncological Outcomes of Patients with High-Volume mCRPC: Results from a Longitudinal Real-Life Multicenter Cohort.

Registrative trials recommended the use of upfront chemotherapy in high-volume metastatic prostate cancer. We reported survival outcomes of patients with high-volume mCRPC treated with ARTA in a chemo-naïve setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. We retrospectively collected data on mCRPC patients treated at six centers. The dataset was queried for high-volume disease (defined as more than 6 bone lesions or bulky nodes ≥ 5 cm). We compared the main clinical features of chemo-naïve versus chemo-treated patients. The Mann-Whitney U test and Chi-squared test were used to compare continuous and categorial variables, respectively. The Kaplan-Meier method was used to compare differences in terms of progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS) in an upfront ARTA or chemo-treated setting. Survival probabilities were computed at 12, 24, 48, and 60 months. Out of 216 patients, 88 cases with high-volume disease were selected. Sixty-nine patients (78.4%) received upfront ARTA, while 19 patients received chemotherapy as the first-line treatment option. Forty-eight patients received Abiraterone (AA), 21 patients received Enzalutamide (EZ) as the first-line treatment. The ARTA population was older (p = 0.007) and less likely to receive further lines of treatment (p = 0.001) than the chemo-treated cohort. The five-year PFS, CSS and OS were 60%, 73.3%, and 72.9%, respectively. Overall, 28 patients (31.8%) shifted after their first-line therapy to a second-line therapy: EZ was prescribed in 17 cases, AA in seven cases and radiometabolic therapy in four patients. Sixteen cases (18.2%) developed significant progression and were treated with chemotherapy. At Kaplan-Meyer analysis PFS, CSS and OS were comparable for upfront ARTA vs chemo-treated patients (log rank p = 0.10, p = 0.64 and p = 0.36, respectively). We reported comparable survival probabilities in a real-life series of high-volume mCRPC patients who either received upfront ARTA or chemotherapy. Patients primarily treated with chemotherapy were younger and more likely to receive further treatment lines than the upfront ARTA cohort. Our data support the use of novel antiandrogens as first line treatment regardless tumor burden, delaying the beginning of a more toxic chemotherapy in case of significant disease progression.

Role of Perilesional Sampling of Patients Undergoing Fusion Prostate Biopsies.

Recently, researchers have proposed perilesional sampling during prostate biopsies to avoid systematic biopsies of patients at risk of prostate cancer. The aim of our study is to evaluate the role of perilesional sampling to avoid systematic biopsies of patients undergoing fusion biopsies. A prospective cohort of patients undergoing transrectal MRI transrectal fusion biopsies were consecutively enrolled. All the patients underwent systematic biopsies (SB), targeted biopsies (TB) and perilesional biopsies within 10 mm from the lesion (PB). The detection rates of different strategies were determined. A total of 262 patients were enrolled. The median age of those enrolled was 70 years. The mean BMI was 27 kg/m2, and the mean and prostate volume was 52 mL. A PIRADS score ≥ 4 was recorded in 163/262 (40%) patients. Overall, the detection rates of cancer were 43.5% (114/262) and 35% (92/262) for csPCa. The use of the target + peri-target strategy resulted in a detection of 32.8% (86/262) of cancer cases and of 29% (76/262) of csPCa cases (Grade Group > 2). Using the target plus peri-target approach resulted in us missing 18/262 (7%) of the csPCa cases, avoiding the diagnosis of 8/262 (3%) of nsPCa cases. A biopsy strategy including lesional and perilesional sampling could avoid unnecessary prostate biopsies. However, the risk of missing significant cancers is present. Future studies should assess the cost-benefit relationship of different strategies.

Adverse events related to darolutamide treatment: analysis of "real life" data from EudraVigilance and the Food and Drug Administration database entries.

BACKGROUND: Aim of our study was to analyze adverse events (AEs) associated with darolutamide using real life data from Eudra-Vigilance (EV) and the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases. METHODS: EV database in European Economic Area (EEA) and the FDA FAERS database were queried to identify darolutamide AEs occurred from 30th July 2019 to May 2022. AEs were recorded in according to category and severity. Real-life data was compared to Aramis registry study. RESULTS: The total number of AEs including data from both databases was 409 reported by FDA-FAERS and 253 reported by EV databases. On registry study, 794 AEs were reported, with serious AEs occurring in 24.8% of patients in the darolutamide group and with 1 death related to trial regimen. The most frequently reported AEs from both database were general disorders (33% and 26%), investigations (19% and 22%), gastrointestinal (15% and 11%), renal and urinary (9%), gastrointestinal (6%) and musculoskeletal disorder (5%). CONCLUSIONS: According to our results darolutamide is safe in a real-life scenario and the most frequent side effect is fatigue. Although up to now there are few reports in both real-life databases, these data are encouraging for clinicians using darolutamide in every day clinical practice.

Adverse events related to alpha-blockers: analysis of real-life data from Eudra-Vigilance.

BACKGROUND: Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs. METHODS: Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30th, 2022. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05). CONCLUSIONS: Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.

Is EMA warning on quinolones and fluoroquinolones really assessed? An EudraVigilance database analysis.

BACKGROUND: On March 11th 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on musculoskeletal and nervous system, with quinolone (QN) and fluoroquinolone (FQ) antibiotics. Aim of this study was to evaluate the effect of the EMA warning on the rate of AEs after QN and FQ treatments, reported in the EudraVigilance (EV) database. METHODS: EV database is the system for managing and analyzing information on suspected AEs to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We retrospectively explored the effect of FQs and QNs on musculoskeletal and nervous system from the EMA warning up to now (21 months) and compared these results with the 21 months before the EMA warning. RESULTS: Main part of AEs in EV database were reported for ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Ciprofloxacin total AEs before 21 months till 12 months of EMA warning were 2763. 12 months before EMA Warning they were 2935. Twelve months after EMA Warning they were 3419. Between 12 months till 21 months they were 3174. Musculoskeletal disorders were respectively 574 (21% of the total) 21 months before, 558 (19%) 12 months before, 1048 (31%) after 12 months, 540 (17%) after 21 months of EMA Warning. Nervous system disorders were respectively 606 (22% of the total) 21 months before, 517 (18%) 12 months before, 680 (20%) after 12 months, 560 (18%) after 21 months of EMA Warning (respectively OR 1,16 95%CI 1,10 -1,22, P 0,12 ; OR 0,76 95%CI 0,69-0,83, P 0,27 ; OR 1,01 95%CI 0,96-1,06 P 0,05). CONCLUSIONS: Our analysis clearly showed no significant differences before and after EMA warning, opening new insights in the role of the EMA warning in clinical practice.