Defining the role of multiparametric MRI in predicting prostate cancer extracapsular extension.

OBJECTIVES: To identify the predictive factors of prostate cancer extracapsular extension (ECE) in an institutional cohort of patients who underwent multiparametric MRI of the prostate prior to radical prostatectomy (RP). PATIENTS AND METHODS: Overall, 126 patients met the selection criteria, and their medical records were retrospectively collected and analysed; 2 experienced radiologists reviewed the imaging studies. Logistic regression analysis was conducted to identify the variables associated to ECE at whole-mount histology of RP specimens; according to the statistically significant variables associated, a predictive model was developed and calibrated with the Hosmer-Lomeshow test. RESULTS: The predictive ability to detect ECE with the generated model was 81.4% by including the length of capsular involvement (LCI) and intraprostatic perineural invasion (IPNI). The predictive accuracy of the model at the ROC curve analysis showed an area under the curve (AUC) of 0.83 [95% CI (0.76-0.90)], p < 0.001. Concordance between radiologists was substantial in all parameters examined (p < 0.001). Limitations include the retrospective design, limited number of cases, and MRI images reassessment according to PI-RADS v2.0. CONCLUSION: The LCI is the most robust MRI factor associated to ECE; in our series, we found a strong predictive accuracy when combined in a model with the IPNI presence. This outcome may prompt a change in the definition of PI-RADS score 5.

PD-L1 immunohistochemical expression in bladder urothelial cancer with SP263, SP142 and 22C3 antibodies: A comparative study.

Programmed death ligand 1 (PD-L1) is currently the only biomarker used for the selection of patients with bladder urothelial cancer for immunotherapy. Several platforms, antibodies and scores are currently available for the evaluation of the expression of PD-L1 in immunohistochemistry (IHC). In this study three different antibodies (SP263, SP142 and 22C3) were compared to establish their performances and concordance rates. Twenty-four consecutive cases of surgically resected urothelial cancers of the bladder were enrolled. All cases were revised, and appropriate tumor areas were selected for IHC. Three commercially available PD-L1 antibodies were tested: 22C3 pharmDx with Dako Autostainer Link 48 (Dako, Carpinteria, Ca), and SP263 and SP142 with the Ventana BenchMark (Ventana Medical Systems, Tucson, AZ) platform. All slides were evaluated by an expert pathologist and both the tumor proportion score (TPS) and the combined positive score (CPS) were determined and compared at two different cut-off levels (≥ 1 and ≥ 10). The SP263 and 22C3 clones produced more positive results with the CPS and TPS scores, respectively. The CPS score identified more positive cases than the TPS score, irrespectively of the clone or the cut-off used; the difference was statistically significant in both the SP263 and SP142 clones with the ≥1 cut-off. No statistically significant differences were found between the clones when the ≥1 cut-off was used, irrespectively of the score. At the contrary, a statistically significant difference (p = 0.024) and a trend to significance (p = 0.082) were respectively found for the TPS and CPS scores, when the SP22C3 and the SP142 clones were compared at a cut-off level of ≥10. The ICC test using CPS was 0.676 and 0.578 for the ≥1 and ≥ 10 cut-offs respectively, and 0.729 and 0.467 respectively for the same cut-offs using TPS. This suggests that the three antibodies under investigation cannot be used interchangeably, especially the 22C3 and SP142 clones which showed statistically significant difference when TPS was tested at a ≥ 10 cut-off.

Initial experience of robot-assisted partial nephrectomy with Hugo™ RAS system: implications for surgical setting.

PURPOSE: Hugo™ RAS system is one of the most promising new robotic platforms introduced in the field of urology. To date, no data have been provided on robot-assisted partial nephrectomy (RAPN) performed with Hugo™ RAS system. The aim of the study is to describe the setting and report the performance of the first series of RAPN performed with Hugo™ RAS system. METHODS: Ten consecutive patients who underwent RAPN at our Institution between February and December 2022 were prospectively enrolled. All RAPN were performed transperitoneally with a modular four-arm configuration. The main outcome was to describe the operative room setting, trocar placement and the performance of this novel robotic platform. Pre, intra and post-operative, variables were recorded. A descriptive analysis was performed. RESULTS: Seven patients underwent RAPN for right-side and three for left-side masses. Median tumor size and PADUA score were 3 (2.2-3.7) cm and 9 (8-9), respectively. Median docking and console time were 9.5 (9-14) and 138 (124-162) minutes, respectively. Median warm ischemia time was 13 (10-14) minutes, and one case was performed clamp-less. Median estimated blood loss was 90 (75-100) mL. One major complication (Clavien-Dindo 3a) occurred. No case of positive surgical margin was recorded. CONCLUSION: This is the first series to prove the feasibility of Hugo™ RAS system in the setting of RAPN. These preliminary results may help new adopters of this surgical platform to identify critical steps of robotic surgery with this platform and explore solutions before in-vivo surgery.

Optimizing decision-making process of benign uretero-enteric anastomotic stricture treatment after radical cystectomy.

PURPOSE: To identify preoperative predictors of endo-urological treatment (EUT) failure while promoting a new diagnostic and therapeutic pathway for benign uretero-enteric anastomosis stricture (UES) management after radical cystectomy (RC). MATERIALS AND METHODS: We relied on a prospectively maintained database including 96 individuals (122 renal units) who developed a benign UES at our institution between 1990 and 2018. UES was classified into two different types according to morphology: FP1 (i.e., sharp or duckbill) and FP2 (i.e., flat or concave). EUT feasibility, success rate, as well as intra and postoperative complications were recorded. Uni- and multivariable logistic regression analysis (MVA) assessed for predictors of EUT failure. RESULTS: Overall, 78 (63.9%) and 32 (26.3%) cases were defined as FP1 and FP2, respectively. EUT was not feasible in 33 (27.1%) cases. After a median follow-up of 50 (IQR 5-240) months, successful treatment was reached only in 15/122 (12.3%) cases. EUT success rates raised when considering short (< 1 cm) (16.8%), FP1 morphology (16.7%) strictures, or the combination of these characteristics (22.4%). Overall, 5 (5.2%) cases had CD ≥ III complications. FP2 (OR: 1.91, 95%CI 1.21-5.31, p = 0.03) and stricture length ≥ 1 cm (OR: 9.08, 95%CI 2.09-65.71, p = 0.009) were associated with treatment failure at MVA. CONCLUSIONS: Endoscopic treatment for benign UES after RC is feasible but harbors a low success rate. Stricture length and radiological morphology of the stricture are related to endoscopic treatment failure. Surgeons should be aware of the stricture features during the preoperative decision-making process to choose the optimal candidate for endoscopic treatment.

The Role of 99mTc-Sestamibi Single-photon Emission Computed Tomography/Computed Tomography in the Diagnostic Pathway for Renal Masses: A Systematic Review and Meta-analysis.

CONTEXT: The diagnostic accuracy of current imaging techniques in differentiating benign from malignant neoplasms in the case of indeterminate renal masses is still suboptimal. OBJECTIVE: To evaluate the diagnostic accuracy of 99mTc-sestamibi (SestaMIBI) single-photon emission tomography computed tomography (SPECT)/CT in characterizing indeterminate renal masses by differentiating renal oncocytoma and hybrid oncocytic/chromophobe tumor (HOCT) from (1) all other renal lesions and (2) all malignant renal lesions. Secondary outcomes were: (1) benign versus malignant; (2) renal oncocytoma and HOCT versus clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma; and (3) renal oncocytoma and HOCT versus chromophobe renal cell carcinoma (chRCC). EVIDENCE ACQUISITION: A literature search was conducted up to November 2022 using the PubMed/MEDLINE, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify eligible studies. Studies included were prospective and retrospective cross-sectional studies in which SestaMIBI SPECT/CT findings were compared to histology after renal mass biopsy or surgery. EVIDENCE SYNTHESIS: Overall, eight studies involving 489 patients with 501 renal masses met our inclusion criteria. The sensitivity and specificity of SestaMIBI SPECT/CT for renal oncocytoma and HOCT versus all other renal lesions were 89% (95% confidence interval [CI] 70-97%) and 89% (95% CI 86-92%), respectively. Notably, for renal oncocytoma and HOCT versus ccRCC and pRCC, SestaMIBI SPECT/CT showed specificity of 98% (95% CI 91-100%) and similar sensitivity. Owing to the relatively high risk of bias and the presence of heterogeneity among the studies included, the level of evidence is still low. CONCLUSIONS: SestaMIBI SPECT/CT has good sensitivity and specificity in differentiating renal oncocytoma and HOCT from all other renal lesions, and in particular from those with more aggressive oncological behavior. Although these results are promising, further studies are needed to support the use of SestaMIBI SPECT/CT outside research trials. PATIENT SUMMARY: A scan method called SestaMIBI SPECT/CT has promise for diagnosing whether kidney tumors are malignant or not. However, it should still be limited to research trials because the level of evidence from our review is low.

Modulation of adipose-derived stem cell behavior by prostate pathology-associated plasma: insights from in vitro exposure.

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.

To drain or not to drain in uro-oncological robotic surgery? A systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to compare the perioperative outcomes of routine drainage insertion vs. no drainage in patients undergoing robot-assisted radical prostatectomy (RARP), robot-assisted partial nephrectomy (RAPN), and robot-assisted radical cystectomy (RARC). EVIDENCE ACQUISITION: A literature search was conducted through April 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. EVIDENCE SYNTHESIS: Eleven studies comprising 8447 RARPs and 1890 RAPNs met our inclusion criteria. Our search strategy did not identify any studies within the RARC framework. In RARP, patients without postoperative drainage had lower rate of postoperative ileus (OR 0.53, 95% CI: 0.38 to 0.74; P<0.001) and similar low-grade (Clavien 1-2, P=0.41) and high-grade (Clavien ≥3; P=0.85) complications, urinary leakage (P=0.07), pelvic hematoma (P=0.35), symptomatic lymphocele (P=0.13), fever (P=0.25), incisional hernia (P=0.31), reintervention (P=0.57), length of hospital stay (P=0.22), and readmission (P=0.74) compared with routinely drained patients. In RAPN, patients without postoperative drainage had shorter length of hospital stay (mean difference: -0.84 days, 95% CI: -1.06 to -0.63; P<0.001) and similar low-grade (P=0.94) and high-grade (P=0.31) complications, urinary leakage (P=0.49), hemorrhage (P=0.39), reintervention (P=0.69), and readmission (P=0.20) compared with routinely drained patients. CONCLUSIONS: In our study, patients without drainage had similar perioperative course to patients with prophylactic drain insertion after RARP and RAPN. Omission of drain insertion was associated with a lower rate of postoperative ileus for RARP and a shorter hospital stay for RAPN. In the era of robotic surgery, routine drain placement is no longer indicated in unselected patients.

Is There an Impact of Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsy in Clinically Significant Prostate Cancer Detection Rate? A Systematic Review and Meta-analysis.

CONTEXT: It is unclear whether a magnetic resonance imaging (MRI)-targeted transperineal (TP) biopsy can improve the detection of clinically significant prostate cancer (csPCa). OBJECTIVE: To compare the MRI-targeted TP and transrectal (TR) approaches for csPCa detection. EVIDENCE ACQUISITION: A literature search was conducted using the PubMed/Medline, Embase, and Web of Science databases to identify reports published until February 2023. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. The primary outcome was the detection of csPCa (Gleason grade group ≥2). Sensitivity analyses were performed to investigate csPCa detection rates according to tumor location, Prostate Imaging Reporting and Data System (PI-RADS) score, and type of fusion (cognitive or software based). EVIDENCE SYNTHESIS: Eleven studies met our inclusion criteria, and data from 3522 and 5140 patients who underwent, respectively, TR and TP MRI-targeted biopsies were reviewed. No statistically significant difference in the detection of csPCa was observed between the TR and TP approaches (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.98-1.25; p = 0.1). When stratifying patients according to lesion location, the TP approach was associated with higher csPCa detection in case of anterior (OR 2.17, 95% CI 1.46-3.22; p < 0.001) and apical (OR 1.86, 95% CI 1.14-3.03; p = 0.01) lesions. In the subgroup analysis based on PI-RADS score, the TP approach was associated with higher csPCa detection (OR 1.57, 95% CI 1.07-2.29; p = 0.02) in PI-RADS 4 lesions. Conversely, no difference was found in PI-RADS 3 and 5 lesions (p > 0.05). The main limitation was the retrospective design of most included studies. CONCLUSIONS: No significant association was found between the prostate biopsy approach and csPCa detection rate when we considered all biopsy indications. The TP approach provides a detection advantage in anterior and apical tumors, arguing for a preferred use of the TP approach in these lesion locations. PATIENT SUMMARY: The transperineal magnetic resonance imaging-targeted prostate biopsy approach appears to be more effective only for selected lesions. No clear benefit was seen for the transperineal approach in the overall population.

Long-Term Oncologic Outcomes of Endoscopic Management of High-Risk Upper Tract Urothelial Carcinoma: The Fundació Puigvert's Experience.

Objectives: Many patients with upper tract urothelial carcinoma (UTUC) outside of the low-risk criteria may possess low absolute risks of distant progression. Herein, we hypothesized that careful selection of high-risk patients undergoing an endoscopic approach could result in acceptable oncologic outcomes. Materials and Methods: Patients with high-risk UTUC managed endoscopically between 2015 and 2021 were retrospectively identified from a prospectively maintained single academic institution database. Elective and imperative indications for endoscopic treatment were considered. Regarding elective indications, the decision to perform endoscopic treatment was systematically proposed to high-risk patients in whom macroscopically complete ablation was deemed feasible, excluding invasive appearance on CT scan, and without histologic variant. Results: A total of 60 patients with high-risk UTUC met our inclusion criteria (29 imperative and 31 elective indications). The median follow-up in patients without any event was 36 months. At 5 years, the estimated overall survival, cancer-specific survival, metastasis-free survival, UTUC recurrence-free survival, radical nephroureterectomy-free survival, and bladder recurrence-free survival were 57% (41-79), 75% (57-99), 86% (71-100), 56% (40-76), 81% (70-93), and 69% (54-88), respectively. All oncologic outcomes were similar between patients with elective and imperative indications (all log-rank p > 0.05). Conclusions: In conclusion, we report the first large series of endoscopic treatment in patients with high-risk UTUC, arguing that promising oncologic outcomes can be achieved in properly selected candidates. We encourage multi-institutional collaborative work as a large cohort of high-risk patients treated endoscopically may allow subgroup analyses to define the best candidates.

Robot-assisted oncologic pelvic surgery with Hugo™ robot-assisted surgery system: A single-center experience.

Objective: To report the outcomes of intra- and extra-peritoneal robot-assisted radical prostatectomy (RARP) and robot-assisted radical cystectomy (RARC) with Hugo™ robot-assisted surgery (RAS) system (Medtronic, Minneapolis, MN, USA). Methods: Data of twenty patients who underwent RARP and one RARC at our institution between February 2022 and January 2023 were reported. The primary endpoint of the study was to report the surgical setting of Hugo™ RAS system to perform RARP and RARC. The secondary endpoint was to assess the feasibility of RARP and RARC with this novel robotic platform and report the outcomes. Results: Seventeen patients underwent RARP with a transperitoneal approach, and three with an extraperitoneal approach; and one patient underwent RARC with intracorporeal ileal conduit. No intraoperative complications occurred. Median docking and console time were 12 (interquartile range [IQR] 7-16) min and 185 (IQR 177-192) min for transperitoneal RARP, 15 (IQR 12-17) min and 170 (IQR 162-185) min for extraperitoneal RARP. No intraoperative complications occurred. One patient submitted to extraperitoneal RARP had a urinary tract infection in the postoperative period that required an antibiotic treatment (Clavien-Dindo Grade 2). In case of transperitoneal RARP, two minor complications occurred (one pelvic hematoma and one urinary tract infection; both Clavien-Dindo Grade 2). Conclusion: Hugo™ RAS system is a novel promising robotic platform that allows to perform major oncological pelvic surgery. We showed the feasibility of RARP both intra- and extra-peritoneally and RARC with intracorporeal ileal conduit with this novel platform.

The Impact of SARS-CoV-2 Pandemic on Time to Primary, Secondary Resection and Adjuvant Intravesical Therapy in Patients with High-Risk Non-Muscle Invasive Bladder Cancer: A Retrospective Multi-Institutional Cohort Analysis.

BACKGROUND: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). METHODS: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG. RESULTS: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups (n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p < 0.0001). CONCLUSIONS: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.