Renorrhaphy techniques in minimally invasive partial nephrectomy: a systematic review of the literature.

INTRODUCTION: In the absence of consensus on the optimal approach to renorrhaphy in partial nephrectomy, this systematic review aims to assess the various renorrhaphy techniques and their impact on surgical outcomes. EVIDENCE ACQUISITION: A systematic review of the literature was performed in March 2022, using PubMed and Scopus, without time restrictions and research filters for studies investigating renorrhaphy techniques in partial nephrectomy. Studies providing sufficient details on renorrhaphy techniques and their outcomes during minimally invasive partial nephrectomy (PN) were included in this analysis. EVIDENCE SYNTHESIS: Thirty-one studies with 5720 patients were included in the analysis. In most studies, tumor diameter was <4 cm. RENAL and PADUA scores as well as tumor locations were heterogeneous between the studies. The results of the use of hemostatic agents were conflicting among different studies with limited evidence regarding the benefits of its routine use in partial nephrectomy. The use of barbed and running sutures was associated with a reduced warm ischemia time. While some studies showed a decreased warm ischemia time when omitting cortical renorrhaphy, others found that it may lead to higher incidence of minor complications without any significant improvement in other outcomes. CONCLUSIONS: There is ongoing research to determine the optimal approach to renorrhaphy. The current evidence on the routine use of hemostatic agents is limited. The use of certain techniques such as barbed sutures, sliding clips and running sutures reduced the warm ischemia time. The omission of cortical renorrhaphy is still controversial.

External validation of biochemical recurrence definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound.

PURPOSE: This is an external validation of several biochemical recurrence definitions based on prostate specific antigen criteria (PSA). The purpose is to predict the need of additional treatment and failure after focal therapy using high intensity focused ultrasound (HIFU) for localized prostate cancer (PCa). MATERIALS AND METHODS: A total of 343 consecutive patients who underwent HIFU with Ablatherm® and Focal One® devices between June 2001 and November 2020 were identified. Treatment failure was defined as clinically significant PCa on postoperative biopsy, the need for salvage radical or systematic treatment, metastasis, or PCa-related death. The biochemical recurrence definitions tested were PSA nadir, time to PSA nadir, percentage of PSA reduction, Huber et al. criteria defined as PSA nadir + 1 ng/mL at 12 months or PSA nadir + 1.5 ng/mL at 24-36 months. Multivariable Cox regression analysis and decision-curve analysis were used to validate and compare criteria. Kaplan-Meier analysis was used to assess criteria associated with the highest accuracy. RESULTS: One hundred seventy-eight patients met the inclusion criteria and were analyzed. Overall, 61 (34%) and 41 (23%) patients had an additional treatment and failure with a median follow-up of 52 months. At multivariable analysis, model including Huber et al. criteria exhibited the highest Harrell's C-index for the prediction of the need of additional treatment (hazard ratio [HR]: 10, p < 0.001, c-index: 84%) and treatment failure (HR: 9.1, p < 0.001, c-index: 82%) as well as higher net benefit. The 60-months need of additional treatment and treatment failure-free survival were 89% and 98% compared to 26% and 49%, respectively, when stratified according to Huber et al. criteria (Log-rank test, p < 0.001). Similar results were found after excluding patient with non-clinically significant PCa at initial biopsy. CONCLUSIONS: We report an external validation of biochemical recurrence definitions predicting the need of additional treatment and failure after focal therapy using HIFU for localized PCa. Huber et al. criteria were identified as the most accurate and could be used to guide clinicians toward further evaluation and salvage treatments.

Do perioperative blood transfusions impact oncological outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion? Results from a large multi-institutional registry.

BACKGROUND: Blood transfusions (BT) have been associated with adverse oncologic outcomes in multiple malignancies including open radical cystectomy (ORC) for urothelial carcinoma of the bladder (UCB). Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) delivers similar oncologic outcomes compared to ORC, yet with lower blood loss and reduced transfusions. However, the impact of BT after robotic cystectomy is still unknown. METHODS: This is a multicenter study including patients treated for UCB with RARC and ICUD in 15 academic institutions, between January 2015 and January 2022. BT were administered during surgery (intraoperative blood transfusions, iBT) or during the first 30 days after surgery (post-operative blood transfusions, pBT). The association of iBT and pBT with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were evaluated by univariate and multivariate regression analysis. RESULTS: A total of 635 patients were included in the study. Overall, 35/635 patients (5.51%) received iBT while 70/635 (11.0%) received pBT. After a mean follow-up of 23±18 months, 116 patients (18.3%) had died, including 96 (15.1%) from bladder cancer. Recurrence occurred in 146 patients (23%). iBT were associated with decreased RFS, CSS and OS (P<0.001) on univariate Cox analysis. After adjusting for clinicopathologic covariates, iBT were associated only with the risk of recurrence (HR: 1.7; 95% CI, 1.0-2.8, P=0.04). pBT were not significantly associated to RFS, CSS or OS on univariate and multivariate Cox regression models (P>0.05). CONCLUSIONS: In the present study, patients treated by RARC with ICUD for UCB have a higher risk of recurrence after iBT, yet no significant association with CSS and OS was found. pBT are not associated with worse oncological prognosis.

Antibody-Drug Conjugates in Prostate Cancer: Where Are we?

Antibody-drug conjugates (ADCs) reflect a new promising approach in prostate cancer, even more so after the practice-changing results in other malignancies, either hematologic or solid. ADCs consist of monoclonal antibodies (mAb) targeted at specific antigens overly expressed on cancer cells compared to normal cells. A cytotoxic payload is attached to the mAb using a stable linker. In prostate cancer, PSMA, STEAP1, TROP2, CD46 and B7-H3 are antigens currently being studied as targets for ADCs. In this paper, we discuss the composition of ADCs and focus on their application and challenges as treatment options in prostate cancer.

Urinary microbiota and prostatic diseases: the key for the lock? A systematic review.

BACKGROUND: Urinary microbiota is implicated in many diseases of the urinary tract. The aim of this study was to perform a systematic review of the role of urinary microbiota in prostatic diseases. METHODS: A PubMed/Medline search was undergone from inception through June 2022 for studies investigating urinary microbiota alterations in prostatic diseases, subdivided into benign prostatic hyperplasia (BPH), prostate cancer (PCa), and chronic prostatitis (CP). Study selection followed the PRISMA statement. Phylum, family, genus and species of each bacterium in cancer patients and controls were recorded. Quality of included studies was evaluated using the Critical Appraisal Skills Program (CASP) checklist for non-randomized studies. RESULTS: A total of 16 studies (4 studies on BPH, 9 studies on PCa and 3 studies on CP) comprising 1486 patients were included in our final analysis. Patients with BPH had a different urinary microbial composition, with a certain pattern proven to be associated with a higher lower urinary tract symptoms severity. Regarding PCa, some bacterial phyla/genera/classes/species were more abundant in PCa and others predicted a higher grade disease. In patients with CP, a different microbiota composition and a higher diversity were found, with the symptom severity being influenced mainly by microbiota composition, favoring aerobic microorganisms. CONCLUSION: Urinary microbiota is implicated in prostatic diseases, especially in BPH, PCa and CP. However, given the relative heterogeneity among published studies, this implication suggests better delineation is needed. Further studies are needed to confirm these findings.

Cost-analysis of robot-assisted radical cystectomy in Europe: A cross-country comparison.

BACKGROUND: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries. METHODS: Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient. RESULTS: A total of 490 patients were included. Median operative time was 300(270-360) minutes and median hospital length-of-stay was 11(8-15) days. The average total cost of RARC was 14.794€ (95%CI 14.300-15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments. CONCLUSION: Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible.

CAR-T Cell Therapy for Solid Tumors: Are we Still That Far? a Systematic Review of Literature.

This systematic review aims to assess all the prospective studies published to date on the efficacy of CAR-T cell therapy in solid tumors. Databases searched were PubMed and Google Scholar from inception through May 1st 2021. Search query was (Chimeric antigen receptor) or (CAR-T) or (T-CAR). Twenty-nine prospective studies (265 patients) were included. Most published clinical trials are phase I. Clinical benefit was 100% in epithelial ovarian cancer, 70-82% in gastrointestinal tumors, 79% in mesothelioma, 63% in small-cell lung cancer, 24-67% in sarcoma, 50-62% in prostate cancer, and 45-50% in central nervous system tumors. No serious CAR-T cell specific serious toxicities were noted.

Defining the Morbidity of Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Adoption of the Comprehensive Complication Index.

Background and Objective: The Clavien-Dindo Classification (CDC) only reports the postoperative complication of highest grade. It is thus of limited value for radical cystectomy, after which patients usually experience multiple complications. The Comprehensive Complication Index (CCI) is a novel scoring system, which incorporates all postoperative events in one single value. The study aimed to adopt the CCI for the evaluation of complications in patients undergoing robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and explore its advantages in the analysis of the morbidity of RARC with ICUD. Patients and Methods: A multicentric cohort of 959 patients undergoing RARC+ICUD between 2015 and 2020, whose complications are encoded in local prospective registries. Postoperative complications at 30 days were assessed using both the CDC and CCI. The CCI was calculated using an online tool (assessurgery.com). Risk factors for overall, major complications (CDC ≥III), and CCI were evaluated using uni- and multivariable logistic and linear regressions. To analyze the potential advantage of using the CCI in clinical trials, a sample size calculation of a hypothetic clinical trial was performed using as endpoint reduction of morbidity with either the CDC or CCI. Results: Overall, 885 postoperative complications were reported in 507 patients (53%). The CCI improved the definition of postoperative morbidity in 22.6% of patients. Male sex and neobladder were associated with major complications and to a significant increase in CCI on adjusted regressions. In a hypothetical clinical trial, 80 patients would be needed to demonstrate a ten-point reduction in CCI, compared with 186 needed to demonstrate an absolute risk reduction of 20% in overall morbidity using the CDC. Conclusion: CCI improves the evaluation of postoperative morbidity by considering the cumulative aspect of complications compared with the CDC. Implementing the CCI for radical cystectomy would help reducing sample sizes in clinical trials. Clinical Trial Registration number: NCT03049410.

Uncovering the role of urinary microbiota in urological tumors: a systematic review of literature.

PURPOSE: Urinary microbiota has been found to play a key role in numerous urological diseases. The aim of this systematic review is to depict the role of urinary microbiota in the pathogenesis, diagnosis, prognosis, and treatment of urological tumors, including bladder cancer (BCa), prostate cancer (PCa) and renal cell carcinoma (RCC). METHODS: A systematic PubMed and Scopus search was undergone from inception through June 2021 for studies investigating urinary microbiota alterations in urological tumors. Study selection followed the PRISMA statement. Phylum, family, genus and species of each bacterium in cancer patients and controls were recorded. RESULTS: Twenty-one studies with 1194 patients (748 cancer patients and 446 controls) were included in our final analysis. Certain bacterial phylum, family, genus, and species were more predominant in each of BCa, PCa and RCC patients compared to controls. Abundance and specificity of urinary microbiota were prognosticators for: (1) recurrence, distinguishing recurrent from non-recurrent BCa, (2) disease stage, distinguishing non-muscle invasive from muscle invasive BCa, and (3) disease grade, distinguishing high- vs. low-grade PCa and BCa. Dietary, environmental and geographic patterns influenced urinary microbiota. Urinary microbiota of benign prostatic hyperplasia was different from PCa. CONCLUSION: Urological cancer patients have an altered urinary microbiota compared to controls. This may predict recurrence, disease stage and disease grade of these tumors. Further prospective studies are needed to depict a potential influence on therapeutic outcomes.

Is pudendal nerve entrapment a potential cause for weak ejaculation?

Ejaculatory dysfunction is one of the most common complaints of patients with sexual disorders. While it encompasses several ejaculatory disorders, weak ejaculation is seldom described in the literature. Since the pudendal nerve is the main nerve of ejaculation, we aim to hypothesize that pudendal nerve entrapment could be a cause of weak ejaculation, and that pudendal nerve release could contribute to the improvement of the ejaculatory stream. We presented two cases suffering from a weak ejaculatory stream and sensation of incomplete semen emptying, accompanied with clinical features of pudendal nerve entrapment. Both cases improved after pudendal nerve block and then laparoscopic transperitoneal pudendal release, with a sustained amelioration of the ejaculatory stream after 3 weeks of surgery. Pudendal canal entrapment is therefore a potentially curable cause for weak ejaculation.

Continuing acetylsalicylic acid during Robotic-Assisted Radical Cystectomy with intracorporeal urinary diversion does not increase hemorrhagic complications: results from a large multicentric cohort.

OBJECTIVES: To evaluate whether continuing the antiplatelet drug acetylsalicylic acid≤100mg (ASA) during Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) increases the risk of peri-and postoperative hemorrhagic complications and overall morbidity. Indeed, guidelines recommend interrupting antiplatelet therapy before radical cystectomy; however, RARC with ICUD is associated to reduced estimated blood loss and blood transfusions compared to its open counterpart. METHODS: Data from a multicentric European database were analyzed. All participating centers maintained a prospective database of patients undergoing RARC with ICUD. We identified patients receiving antiplatelet therapy by acetylsalicylic acid ≤100mg. Patients were divided into three groups: those not taking acetylsalicylic acid (no-ASA), those where ASA was continued perioperatively (c-ASA) and those where ASA was interrupted perioperatively (i-ASA). Estimated blood loss and peri-and post-operative transfusions were recorded. Hemorrhagic complications, ischemic, thrombotic and cardiac morbidity was recorded and classified using the Clavien-Dindo score by a senior urologist. RESULTS: 640 patients were analyzed. Patients on acetylsalicylic acid were significantly older and had more comorbidities. No significant difference was found for estimated blood loss between no-ASA, c-ASA and i-ASA (280 vs. 300 vs. 200ml respectively; P = 0.09). Similarly, no significant difference was found for intraoperative (5% vs. 9% vs. 11%; P = 0.07) and postoperative transfusion rate (11% vs. 13% vs. 18%; P = 0.17). Higher ischemic complications were noted in the i-ASA group compared to no-ASA and c-ASA (4% vs. 0.6% vs. 1.4%; P = 0.03). On uni and multivariate logistic regression, continuing acetylsalicylic acid was not significantly associated to either major complications or post-operative transfusions. CONCLUSIONS: Peri-operative acetylsalicylic acid continuation in RARC with ICUD does not increase hemorrhagic complications. Interrupting acetylsalicylic acid peri-operatively may expose patients to a higher risk of ischemic events.

Anterior vs. Retzius-sparing robotic assisted radical prostatectomy: can the approach really make a difference?

INTRODUCTION: Retzius-sparing Robotic Assisted Radical Prostatectomy (RS-RARP) is a novel surgical approach to radical prostatectomy. Its pioneers have suggested an improved recovery of urinary continence, while maintaining adequate cancer control. The aim of this systematic review was to explore available data on RS-RALP and compare functional, oncologic, and perioperative results of RS-RARP compared to anterior RARP. EVIDENCE ACQUISITION: A search following PRISMA guidelines was performed including the combination of the following words: "Retzius" AND "sparing" AND "radical" AND "prostatectomy." Ninety-three articles were identified and 13 were included in the systematic review, including 3 randomized controlled trials (RCT), 4 prospective studies and 6 retrospective studies. EVIDENCE SYNTHESIS: All available randomized trials confirmed an improved immediate continence for RS-RARP, with rates ranging 51-71%, compared to 21-48% for anterior RARP. However, this advantage was progressively lost with no significant difference found after 6 months. Moreover, a prospective study found no discrepancy in terms of quality of life across the two techniques. Erectile function was difficult to compare, as patients had different baseline erectile function across studies and rate of neurovascular preservation was not comparable. Surgical approach remains controversial regarding positive margin rate, although related to the surgeon's experience and clinical stage. Biochemical recurrence-free survival appears similar between the two approaches. CONCLUSIONS: RS-RARP improves early urinary continence recovery compared to anterior RARP, with this advantage being lost after 3 to 6 months. Erectile function and quality of life were however comparable between the two techniques. The results concerning the rate of positive margins remained controversial. Future studies with longer follow-up are needed to better assess oncologic outcomes.

Urothelial carcinoma in COVID-19: lessons from a pandemic and their impact on clinical practice.

The COVID-19 pandemic has modified the management of urothelial carcinoma (UC). Eighteen months after the onset of the pandemic, a scoping narrative review was able to state that radical cystectomy for UC should not be delayed beyond 10 weeks when neoadjuvant chemotherapy (NAC) was administered and 12 weeks when it was not. NAC should be considered when imminent chemotherapy cannot be performed. Early cystectomy should not be delayed when indicated for patients with high-risk non-MIBC. Patients with non-MIBC should still receive their induction doses of intravesical instillations. Diagnostic cystoscopy should not be deferred in symptomatic patients. Surgical management of upper tract urothelial carcinoma (UTUC) allows for a wider deferral interval.

Antibodies targeting Prostate-Specific Membrane Antigen positive prostate cancer: from diagnostic imaging to theranostics.

PURPOSE OF REVIEW: Targeting Prostate-Specific Membrane Antigen (PSMA) has paved the way for personalized medicine in prostate cancer (PCa) patients. This review aims to highlight the role of PSMA targeting antibodies in PCa, for diagnostic and therapeutic purposes. RECENT FINDINGS: PSMA Positron Emission Tomography/Computed Tomography has been a game changer in the diagnosis of PCa in the recent decade. Two anti-PSMA monoclonal antibodies have been studied in PCa: 7E11-C35 (limited use) and J591. J591 antibody was used for diagnostic purposes coupled with different radionuclides. Most importantly, it was combined to numerous therapeutic radionuclides such as Lutetium-177 (177Lu), Yttrium-90 (90Y), Indium-111 (111In), and Actinium-225 (225Ac). It was also conjugated to drugs forming antibody-drug conjugates (e.g. MLN2704 and PSMA-ADC). These compounds were tested in recent phase I/II clinical trials. SUMMARY: PSMA targeting antibodies are very promising for further clinical investigation and continue to be a momentous research area, for both imaging and therapeutic settings. Although some clinical trials resulted in unfavorably safety profiles for some antibodies, they validated PSMA as a crucial immunoconjugate target.