Research protocol for an observational health data analysis to assess the applicability of randomized controlled trials focusing on newly diagnosed metastatic prostate cancer using real-world data: PIONEER IMI's "big data for better outcomes" program.

Background: Metastatic prostate cancer (PCa) constitutes ~5% of all new PCa diagnoses in Western countries. For most cases, primary consideration should be given to systemic therapies as the first-line approach based on evidence from randomized controlled trials (RCTs). Despite the importance of RCTs as the pinnacle of evidence in modern medicine, concerns have been raised about their applicability to real-life scenarios. These trials often feature participants who are younger with better performance statuses and prognoses compared to their real-world counterparts. The PIONEER project falls under the Innovative Medicine Initiative's (IMI) "Big Data for Better Outcomes" initiative, aimed at revolutionizing PCa care in Europe. The central focus lies in improving cancer-related outcomes, enhancing health system efficiency, and elevating the quality of health and social care. This study endeavours to evaluate the generalizability of RCT findings concerning newly diagnosed metastatic PCa. Methods: A systematic review of the literature will be conducted to compile patient characteristics from RCTs addressing this subject within the past decade. To create a real-world benchmark, patients with recently diagnosed metastatic PCa from a network of population-based databases will serve as a comparison group. The objective is to assess the applicability of RCT results in two ways. First, a comparison will be made between the characteristics of patients with newly diagnosed metastatic PCa enroled in RCTs and those with the same condition included in our databases which might represent the real-world setting. Second, an evaluation will be undertaken to determine the proportion of real-world patients with newly diagnosed metastatic PCa who meet the criteria for RCT enrolment. This study will rely on extensive observational data, primarily sourced from population-based registries, electronic health records, and insurance claims data. The study cohort is established upon routinely gathered healthcare data, meticulously mapped to the Observational Medical Outcomes Partnership Common Data Model.

Patient-reported Outcome Measures and Experience Measures After Active Surveillance Versus Radiation Therapy Versus Radical Prostatectomy for Prostate Cancer: A Systematic Review of Prospective Comparative Studies.

BACKGROUND AND OBJECTIVE: Current management options for localized prostate cancer (PCa) include radical prostatectomy (RP), radiotherapy (RT), and active surveillance (AS). Despite comparable oncological outcomes, there is still lack of evidence on their comparative effectiveness in terms of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). We conducted a systematic review of studies comparing PROMs and PREMs after all recommended management options for localized PCa (RP, RT, AS). METHODS: A literature search was performed in the MEDLINE, EMBASE, and Cochrane CENTRAL databases in accordance with recommendations from the European Association of Urology Guidelines Office and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All prospective clinical trials reporting PROMs and/or PREMs for comparisons of RP versus RT versus AS were included. A narrative synthesis was used to summarize the review findings. No quantitative synthesis was performed because of the heterogeneity and limitations of the studies available. KEY FINDINGS AND LIMITATIONS: Our findings reveal that RP mostly affects urinary continence and sexual function, with better results for voiding symptoms in comparison to other treatments. RT was associated with greater impairment of bowel function and voiding symptoms. None of the treatments had a significant impact on mental or physical quality of life. Only a few studies reported PREMs, with a high rate of decision regret for all modalities (up to 23%). CONCLUSIONS AND CLINICAL IMPLICATIONS: All recommended treatments for localized PCa have an impact on PROMs and PREMs, but for different domains and with differing severity. We found significant heterogeneity in PROM collection, so standardization in real-world practice and clinical trials is warranted. Only a few studies have reported PREMs, highlighting an unmet need that should be explored in future studies. PATIENT SUMMARY: We reviewed differences in patient reports of their outcomes and experiences after surgical prostate removal, radiotherapy, or active surveillance for prostate cancer. We found differences in the effects on urinary, bowel, and sexual functions among the treatments, but no difference for mental or physical quality of life. Our results can help doctors and prostate cancer patients in shared decision-making.

Predictive Models for Assessing Patients' Response to Treatment in Metastatic Prostate Cancer: A Systematic Review.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients' response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Research Protocol for an Observational Health Data Analysis on the Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-sensitive Prostate Cancer: Big Data Analytics Using the PIONEER Platform.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Impact of minimally invasive surgical procedures for Male Lower Urinary Tract Symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review.

BACKGROUND: Surgical treatments for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are affected by potentially bothersome side effects on sexual, and, above all, ejaculatory function. Several minimally invasive techniques have been proposed in the last years in order to overcome these consequences. Our aim is to summarize and evaluate the efficacy on LUTS relieve and the impact on sexual/ejaculatory function of Rezum, prostate artery embolization (PAE), implantation of a prostatic urethral lift (PUL) and the temporary implantable nitinol device (TIND). METHODS: A systematic review of the English-language literature was conducted using the MEDLINE, Embase, and Web of Science databases from January 2000 to October 2022, according to the PRISMA guidelines (PROSPERO ID: CRD42023466515). Randomized controlled trials (RCTs), prospective studies and non-comparative or comparative studies assessing the impact on functional and ejaculatory function after minimally invasive surgical therapies for Male LUTS were evaluated. Risk of bias assessment was performed according to the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for comparative studies, and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs. RESULTS: Overall, 47 studies were included (n = 4 for TIND; n = 9 for Rezum; n = 13 for PUL; n = 21 for PAE). Most studies relied on prospective patient cohorts and were rated as low risk of bias. Across studies assessing the efficacy of Rezum, a significant improvement in terms of IPSS (ranging from -47% to -56%) and Qmax (ranging from +39% to +87%) was reported. On the other hand, according to IIEF-5 score, Rezum had a minimal impact on sexual function (ranging from -1% to -3%). PUL showed a positive impact on IPSS (ranging from -35% to -58.2%) and Qmax (ranging from +49.9% to +114.7%) and sexual function. Finally, PAE showed encouraging functional results with IPSS score reducing from -12.8% to 63.3% and Qmax improving from +8% to 114.9% but the available evidence regarding the potential impact of PAE on sexual outcomes were limited. CONCLUSION: Rezum, PAE, PUL and TIND are safe and feasible techniques associated with a significant functional improvement. While available data suggest a minimal impact of Rezum and PUL on ejaculatory function, the evidence after PAE and TIND are still limited. Therefore, our review lays the foundation for further research aiming to identify the criteria to select best candidates for uMIST to tailor the management in light of specific patient- and disease- factors.

The Oncological and Functional Prognostic Value of Unconventional Histology of Prostate Cancer in Localized Disease Treated with Robotic Radical Prostatectomy: An International Multicenter 5-Year Cohort Study.

BACKGROUND AND OBJECTIVE: The impact of prostate cancer of unconventional histology (UH) on oncological and functional outcomes after robot-assisted radical prostatectomy (RARP) and adjuvant radiotherapy (aRT) receipt is unclear. We compared the impact of cribriform pattern (CP), ductal adenocarcinoma (DAC), and intraductal carcinoma (IDC) in comparison to pure adenocarcinoma (AC) on short- to mid-term oncological and functional results and receipt of aRT after RARP. METHODS: We retrospectively collected data for a large international cohort of men with localized prostate cancer treated with RARP between 2016 and 2020. The primary outcomes were biochemical recurrence (BCR)-free survival, erectile and continence function. aRT receipt was a secondary outcome. Kaplan-Meier survival and Cox regression analyses were performed. KEY FINDINGS AND LIMITATIONS: A total of 3935 patients were included. At median follow-up of 2.8 yr, the rates for BCR incidence (AC 10.7% vs IDC 17%; p < 0.001) and aRT receipt (AC 4.5% vs DAC 6.3% [p = 0.003] vs IDC 11.2% [p < 0.001]) were higher with UH. The 5-yr BCR-free survival rate was significantly poorer for UH groups, with hazard ratios of 1.67 (95% confidence interval [CI] 1.16-2.40; p = 0.005) for DAC, 5.22 (95% CI 3.41-8.01; p < 0.001) for IDC, and 3.45 (95% CI 2.29-5.20; p < 0.001) for CP in comparison to AC. Logistic regression analysis revealed that the presence of UH doubled the risk of new-onset erectile dysfunction at 1 yr, in comparison to AC (grade group 1-3), with hazard ratios of 2.13 (p < 0.001) for DAC, 2.14 (p < 0.001) for IDC, and 2.01 (p = 0.011) for CP. Moreover, CP, but not IDC or DAC, was associated with a significantly higher risk of incontinence (odds ratio 1.97; p < 0.001). The study is limited by the lack of central histopathological review and relatively short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS: In a large cohort, UH presence was associated with worse short- to mid-term oncological outcomes after RARP. IDC independently predicted a higher rate of aRT receipt. At 1-yr follow-up after RP, patients with UH had three times higher risk of erectile dysfunction post RARP; CP was associated with a twofold higher incontinence rate. PATIENT SUMMARY: Among patients with prostate cancer who undergo robot-assisted surgery to remove the prostate, those with less common types of prostate cancer have worse results for cancer control, erection, and urinary continence and a higher probability of receiving additional radiotherapy after surgery.

Research protocol to identify progression and death amongst patients with metastatic hormone-sensitive prostate cancer treated with available treatments: PIONEER IMI's "big data for better outcomes" program.

Androgen deprivation therapy-based with or without first-generation anti-androgens, was the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) for decades. However, the development of docetaxel chemotherapy and new androgen receptor-targeted agents, abiraterone acetate and prednisolone, apalutamide , enzalutamide and darolutamide (in combination with docetaxel chemotherapy) has proven that combination of treatments is more effective. Recently, intensification therapy, so-called "triplets", have emerged in the armamentarium of mHSPC treatment. Metastatic disease is a clinical state that remains poorly understood. The optimal diagnostic and management of patients with mHSPC are changing thanks to the development of new imaging techniques and therapies. The primary objective of this study is to develop and validate a predictive model for the occurrence of symptomatic progression, initiation of new treatments and death amongst patients with mHSPC treated with one of the approved treatment plans, on characteristics present at admission.

Morbidity of Transrectal MRI-Fusion Targeted Prostate Biopsy at a Tertiary Referral Academic Centre: An Audit to Guide the Transition to the Transperineal Approach.

Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien-Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway.

Will Aquablation Be the New Benchmark for Robotic Minimally Invasive Surgical Treatment for Benign Prostatic Hyperplasia?

BACKGROUND AND OBJECTIVE: Aquablation is included in the European Association Urology guidelines as an alternative surgical technique for prostate resection. The evidence summary states that it is subjectively and objectively as effective as transurethral resection of the prostate (TURP) and enucleation, but concerns remain regarding postoperative bleeding. Our aim was to provide an evidence-based overview of the trials, triumphs, and technical challenges of Aquablation. METHODS: A literature search in the PubMed, EMBASE, and Scopus databases was performed to identify clinical prospective and retrospective studies and reviews on Aquablation. A total of 54 reports were included. A narrative review of current evidence and an overview of the surgical technique are provided. KEY FINDINGS AND LIMITATIONS: Aquablation demonstrates excellent short- and long-term functional outcomes, with a good safety profile comparable to that of TURP. The procedure is efficient and safe, even for very large prostates, with sustained improvements in functional outcomes well maintained up to 5 yr. The unique ability to conduct robotically controlled precise ablation of enlarged tissue while maintaining the sphincter makes Aquablation a very good ejaculation-sparing BPH treatment option. Initial issues with hemostasis have been successfully overcome with the use of gentle bladder-neck cautery after the procedure, allowing for early catheter removal. The above features make Aquablation an attractive minimally invasive technique and show that it is noninferior to holmium laser enucleation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Aquablation is a valid alternative to standard resection techniques, showing excellent long-term functional outcomes, good preservation of sexual function, a good safety profile, and good compliance for all prostate sizes and patient ages. Aquablation is still performed in high-volume centers, but the results can easily be emulated in other centers worldwide. ADVANCING PRACTICE: Our review indicates that if Aquablation outcomes are emulated globally, this technique could easily become a new benchmark in robotic treatment for BPH. PATIENT SUMMARY: Aquablation is a safe and effective surgical technique for treatment for benign enlargement of the prostate, with excellent medium-term outcomes. Although long-term studies are needed, the results are promising and challenge the current surgical and laser techniques used to reduce the size of the prostate gland.

A Territory-wide Study Investigating the Dose and Efficacy of Different Bacillus Calmette-Guérin Strains in Patients with Intermediate- and High-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND: Current European Association of Urology (EAU) guidelines support adjuvant intravesical Bacillus Calmette-Guérin (BCG) treatment after Transurethral Resection of Bladder Tumor (TURB) for intermediate- or high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients, aiming to reduce the risk of tumor recurrence. The quality of data, however, does not allow definitive conclusions on whether different strains and dosages of BCG have different efficacies on long-term survival outcomes. OBJECTIVE: To evaluate the long-term survival outcomes of different strains and dosages of BCG in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: All NMIBC patients treated with intravesical BCG therapy from 2001 to 2020 were identified using a territory-wide database in Hong Kong. INTERVENTION: BCG strains and dosages (Connaught strain 81 mg, Connaught strain 27 mg, Tokyo strain 80 mg, and Danish strain 30 mg) were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. A multivariable Cox regression analysis was used to adjust potential confounding factors, and to estimate Hazard Ratio (HR) and 95% confidence interval (CI) of different BCG strains. A further subgroup analysis on adequate versus inadequate BCG treatment was performed. RESULTS AND LIMITATIONS: A total of 2602 NMIBC patients treated with intravesical BCG were identified. Among them, 1291 (49.6%) received Connaught strain 81 mg, 199 (7.6%) received Connaught strain 27 mg, 1014 (39.0%) received Tokyo strain, and 98 (3.8%) received Danish strain. The median follow-up was 11.0 years. No statistically significant differences in OS, CSS, RFS, and PFS were detected among the different groups. At the multivariable analysis, the Connaught strain 27 mg group was inferior to the Connaught strain 81 mg group in terms of OS (HR: 1.26, 95% CI: 1.05-1.51), CSS (HR: 1.69, 95% CI: 1.08-2.66), and PFS (HR: 1.86, 95% CI: 1.20-2.88). Adequate BCG treatment was associated with improved OS (HR: 0.82, 95% CI: 0.73-0.92), CSS (HR: 0.64, 95% CI: 0.47-0.86), RFS (HR: 0.80, 95% CI: 0.70-0.92), and PFS (HR: 0.52, 95% CI: 0.39-0.68). Among patients treated with adequate BCG, at the multivariable analysis the Connaught strain 27 mg group showed worse results than the Connaught strain 81 mg group in terms of CSS (HR: 1.93, 95% CI: 1.07-3.51). Compared with the Connaught strain 81 mg group, both Tokyo and Danish strains had similar survival outcomes in the whole cohort and the adequate BCG treatment subgroup. CONCLUSIONS: Our findings suggest that adequate BCG remains the most important factor in optimizing survival outcomes in patients with intermediate- and high-risk NMIBC. No significant differences in survival outcomes were observed between full-dose Connaught, Tokyo, and Danish strains. Reduced-dose Connaught strain was associated with the worst survival outcomes. PATIENT SUMMARY: We evaluated the efficacy of different strains and dosages of bacillus Calmette-Guérin (BCG) in patients with intermediate- or high-risk non-muscle-invasive bladder cancer in the past two decades in Hong Kong. We conclude no significant differences in long-term survival outcomes in terms of full-dose Connaught, Tokyo, and Danish strains, while reduced-dose Connaught strain was inferior to the full-dose group. Adequate BCG treatment benefits long-term survival.

En bloc resection of bladder tumour: the rebirth of past through reminiscence.

PURPOSE: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. METHODS: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. RESULTS: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. CONCLUSION: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice.

Functional outcomes and safety of focal therapy for prostate cancer: a systematic review on results and patient-reported outcome measures (PROMs).

INTRODUCTION: Focal therapy (FT) is a promising alternative with curative intent for Low- to Intermediate-risk localized Prostate Cancer (PCa), claiming better functional outcomes and safety profile than standard whole-gland treatments. Ten different FT modalities have been described in the literature. The objective of our narrative review is to evaluate the safety profile and functional outcomes of these different modalities and the current most used tools of assessment for those outcomes. MATERIAL AND METHODS: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole-gland treatments were excluded. All articles reporting functional outcomes were included. RESULTS: One-hundred-seven studies, reporting data on 6933 patients, were included (26 on High Intensity Focal Ultrasound, 22 on Focal Cryotherapy, 14 on Irreversible Electroporation, 11 on Focal brachytherapy, 10 on Focal Laser Ablation, 8 on Photodynamic Therapy, 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation, 1 on Prostatic Artery Embolization, and 7 studies comparing different FTs). Post-operative pad-free rate ranged between 92.3-100%. Greater heterogeneity exists considering the Change in Erectile Function, with Changing in Erectile function- rates ranging between 0-94.4% (Cryotherapy). The most used Patient-Reported Outcome Measures (PROMs) were the International Prostate Symptom Score and the International Index of Erectile Function for incontinence/urinary function and potency, respectively. The most common reported complications were hematuria, infections, and urethral strictures, with rates widely ranging among different treatments. The Clavien-Dindo Classification was the most used (40/88 papers) to describe adverse events. CONCLUSION: FT is a promising treatment for localized PCa, achieving excellent results in terms of safety and functional outcomes. There is a wide heterogeneity in the definition of PROMS and time of collection between studies. High quality comparative studies with standard treatments are needed to reinforce these findings.

Oncological results and cancer control definition in focal therapy for Prostate Cancer: a systematic review.

INTRODUCTION: Focal therapy (FT) is a promising alternative to whole-gland treatments for Localized Prostate Cancer. Ten different FT modalities have been described in literature. However, FT is not yet recommended by the International Guidelines, due to the lack of robust data on Oncological Outcomes. The objective of our Narrative Review is to evaluate the oncological profile of the available FT modalities and to offer a comprehensive overview of the definitions of Cancer Control for FT. MATERIAL AND METHODS: Literature search was performed on 21st February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole gland-treatments were excluded. All articles reporting oncological outcomes were included. RESULTS: One-hundred-twenty-four studies, reporting data on more than 8000 patients treated with FT, were included. Overall, 40 papers were on High Intensity Focal Ultrasound (HIFU), 24 on Focal Cryotherapy, 13 on Irreversible Electroporation (IRE), 11 on Focal brachytherapy, 10 on Focal Laser Ablation (FLA), 8 on Photo-Dynamic Therapy (PDT), 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation (bRFA), 1 on Prostatic Artery Embolization (PAE) and 9 comparative papers. Overall, the Biochemical Recurrence (BCR) rate ranged from 0% (Focal Brachytherapy) to 67.5% (HIFU); the Salvage treatment rate ranged from 1% (IRE) to 54% (HIFU) considering re-treatment with FT and from 0% (Focal Brachytherapy) to 66.7% considering standard Radical Treatments. There is no univocal definition of Cancer Control, however the "Phoenix criteria" for BCR were the most commonly used. CONCLUSIONS: FT is a promising alternative treatment for localized prostate cancer in terms of Oncological Outcomes, however there is a wide heterogeneity in the definition of cancer control, the reporting of oncological outcomes and a lack of high-quality clinical trials. Solid comparative studies with standard treatments and an unambiguous consensus on how to describe Cancer Control in the field of Focal Therapy are needed.

Current Techniques for En Bloc Transurethral Resection of Bladder Tumor: A Hands-on Guide Through the Energy Landscape.

En bloc resection of bladder tumor (ERBT) has attracted interest as a potentially superior technique to transurethral resection of bladder tumor (TURBT) to obtain detrusor muscle in the specimen. Different ERBT techniques have been described, with bipolar electrocautery and laser being the more favored energy modalities. Electrocautery EBRT has an advantage in terms of widespread availability in clinics and ease of conversion to piecemeal resection in case of large bladder tumors in different locations. Laser EBRT has an advantage in preventing obturator nerve reflex, which is particularly useful for lateral wall tumors. Further research is needed to assess the potential case-related advantages of the ERBT techniques over each other. PATIENT SUMMARY: Surgical removal of a bladder tumor as a whole single piece, called en bloc resection, is a safe procedure for the diagnosis and treatment of noninvasive bladder cancer. In this mini-review we summarize the evidence for current techniques for en bloc resection.

Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2.

BACKGROUND: Extensive research effort has been devoted to investigating the link between inflammation and PCa. However, this relationship remains unclear and controversial. The aim of our multi-center study was to investigate this association by histologically evaluating the distribution of PI and PCA in prostate biopsy cores from patients of eight referral centers in Italy. RESULTS: We evaluated 2220 cores from 197 patients; all the frustules were re-evaluated by dedicated pathologists retrospectively. Pathologists assigned IRANI scores and determined the positions of PIs; pathologists also re-evaluated the presence of PCa and relative ISUP grade. PCa was recorded in 749/2220 (33.7%). We divided this sample into a PCa PI group (634/749 cores [84.7%]) and a non-PCa + PI group (1157/1471 cores [78.7%]). We observed a statistically significant difference in the presence of inflammation among cores with cancer (p < 0.01). Moreover, periglandular inflammation was higher in the cores with neoplasia, while stromal inflammation was higher in cores without neoplasia (38.5% vs. 31.1% and 55.4% vs. 63.5% p < 0.01). CONCLUSIONS: In our experience, there is evidence of an association between PI and PCa at a tissue level. Further studies are needed to confirm our findings and to identify patients who might benefit from target therapies to prevent PCa occurrence and/or progression.

Urinary Continence Recovery after Robotic Radical Prostatectomy without Anterior or Posterior Reconstruction: Experience from a Tertiary Referral Center.

BACKGROUND: The aim of our study is to evaluate the prevalence and predictive factors of short- (30 d) and mid-term continence in a contemporary cohort of patients treated with robotic-assisted laparoscopic prostatectomy (RALP) without any posterior or anterior reconstruction at our referral academic center. METHODS: Data from patients undergoing RALP between January 2017 and March 2021 were prospectively collected. RALP was performed by three highly experienced surgeons following the principles of the Montsouris technique, with a bladder-neck-sparing intent and maximal preservation of the membranous urethra (if oncologically safe) without any anterior/posterior reconstruction. (Self-assessed urinary incontinence (UI) was defined as the need of one or more pads per die (excluding the need for a safety pad/die. Univariable and multivariable logistic regression analysis was used to assess the independent predictors of early incontinence among routinely collected patient- and tumor-related variables). RESULTS: A total of 925 patients were included; of these, 353 underwent RALP (38.2%) without nerve-sparing intent. The median patient age and BMI were 68 years (IQR 63-72) and 26 (IQR 24.0-28.0), respectively. Overall, 159 patients (17.2%) reported early (30 d) incontinence. In multivariable analysis adjusting for patient- and tumor-related features, a non-nerve-sparing procedure (OR: 1.57 [95% CI: 1.03-2.59], p = 0.035) was independently associated with the risk of urinary incontinence in the short-term period, while the absence of cardiovascular diseases before surgery (OR: 0.46 [95% CI: 0.320.67], p ≤ 0.01) was a protective factor for this outcome. At a median follow-up of 17 months (IQR 10-24), 94.5% of patients reported to be continent. CONCLUSIONS: In experienced hands, most patients fully recover urinary continence after RALP at mid-term follow-up. On the contrary, the proportion of patients who reported early incontinence in our series was modest but not negligible. The implementation of surgical techniques advocating anterior and/or posterior fascial reconstruction might improve the early continence rate in candidates for RALP.

The role of COVID-19 in prostate tissue inflammation: first pathological evidence.

According to current studies, COVID-19 might have an impact on semen quality. Therefore, SARS-CoV-2 may affect other traits of male reproductive system, including the prostate. Thus, we recruited patients who experienced COVID-19 infection in-between prostate biopsy and radical prostatectomy and compared prostate samples inflammation, measured with IRANI score, to those who did not. Indeed, we recruited 20 patients, aged 69 (62-73) years, finding no difference between the 10 patients with COVID-19 infection and the others in IRANI score and all its sub-scores. Hence, according to our exploratory and limited results, COVID-19 infection might have no gross effect on prostate inflammation.

Male reproductive system inflammation after healing from coronavirus disease 2019.

BACKGROUND: There is evidence that, after severe acute respiratory syndrome coronavirus 2 infection, male reproductive function and semen quality may be damaged OBJECTIVES: To evaluate a panel of inflammatory mediators in semen in patients recovered from coronavirus disease 2019. MATERIAL AND METHODS: Sexually active men with previous severe acute respiratory syndrome coronavirus 2 infection and proven recovery from coronavirus disease 2019 were enrolled in a prospective cohort study. Clinical, uro-andrological data and semen specimens were prospectively collected. For previously hospitalized coronavirus disease 2019 patients, data on serum inflammatory markers were retrospectively collected. RESULTS: A total of 43 men were enrolled in the study. Of these, 32 men were normozoospermic, three were oligozoospermic, and eight were crypto-azoospermic. Serum inflammatory markers (procalcitonin and C-reactive protein) were analyzed in previously hospitalized patients both at admission and at peak of infection. Levels at admission were statistically significantly higher in patients resulting in crypto-azoospermic with respect to those resulting in normozoospermic (p = 0.05; p = 0.03 and p = 0.02, respectively) after healing. Seminal cytokine levels were similar among all groups. Interleukin-1ß and tumor necrosis factor-α levels were significantly negatively related to sperm total number and concentration, whereas interleukin-4 was correlated with sperm motility. DISCUSSION AND CONCLUSION: Negative correlations between interleukin-1ß and tumor necrosis factor-α and sperm number and the overall high levels of semen cytokines indicate a potential detrimental role of severe acute respiratory syndrome coronavirus 2 driven inflammation on spermatogenesis. Overall, our results indicate that male patients recovering from coronavirus disease 2019 deserve accurate follow-up for their fertility status.

Case Report: Optimizing Pre- and Intraoperative Planning With Hyperaccuracy Three-Dimensional Virtual Models for a Challenging Case of Robotic Partial Nephrectomy for Two Complex Renal Masses in a Horseshoe Kidney.

Objective: To report a case of robot-assisted partial nephrectomy (RAPN) for two highly complex renal tumors in a patient with a Horseshoe kidney (HSK), focusing on the utility of hyperaccuracy three-dimensional (HA3D) virtual models for accurate preoperative and intraoperative planning of the procedure. Methods: A 74-year-old Caucasian male patient was referred to our Unit for incidental detection of two complex renal masses in the left portion of a HSK. The 50 × 55 mm, larger, predominantly exophytic renal mass was located at the middle-lower pole of the left-sided kidney (PADUA score 9). The 16 × 17 mm, smaller, hilar renal mass was located at the middle-higher pole of the left-sided kidney (PADUA score 9). Contrast-enhanced CT scan images in DICOM format were processed using a dedicated software to achieve a HA3D virtual reconstructions. RAPN was performed by a highly experienced surgeon using the da Vinci Si robotic platform with a three-arm configuration. A selective delayed clamping strategy was adopted for resection of the larger renal mass while a clampless strategy was adopted for the smaller renal mass. An enucleative resection strategy was pursued for both tumors. Results: The overall operative time was 150 min, with a warm ischemia time of 21 min. No intraoperative or postoperative complications were recorded. Final resection technique according to the SIB score was pure enucleation for both masses. At histopathological analysis, both renal masses were clear cell renal cell carcinoma (ccRCC) (stage pT1bNxMx and pT3aNxMx for the larger and smaller mass, respectively). At a follow-up of 7 months, there was no evidence of local or systemic recurrence. Conclusions: Surgical management of complex renal masses in patients with HSKs is challenging and decision-making is highly nuanced. To optimize postoperative outcomes, proper surgical experience and careful preoperative planning are key. In this regard, 3D models can play a crucial role to refine patient counseling, surgical decision-making, and pre- and intraoperative planning during RAPN, tailoring surgical strategies and techniques according to the single patient's anatomy.