Perioperative Outcomes of Robotic Radical Prostatectomy with Hugo™ RAS versus daVinci Surgical Platform: Propensity Score-Matched Comparative Analysis.

Background/Objectives: There is an urgent need for comparative analyses of the intraoperative, oncological, and functional outcomes of different surgical robotic platforms. We aimed to compare the outcomes of RARP performed at a tertiary referral robotic centre with the novel HugoTM RAS system with those performed with a daVinci surgical system, which is considered the reference standard. Methods: We analysed the data of 400 patients undergoing RARP ± pelvic lymph node dissection between 2021 and 2023, using propensity score (PS) matching to correct for treatment selection bias. All procedures were performed by three surgeons with HugoTM RAS or daVinci. Results: The PS-matched cohort included 198 patients with 99 matched pairs, balanced for all covariates. Positive surgical margins (PSMs) were found in 22.2% and 25.3% (p = 0.616) of patients, respectively, in the HugoTM RAS and daVinci groups. No significant differences were found for other important perioperative outcomes, including median (1st-3rd q) operative time (170 (147.5-195.5) vs. 166 (154-202.5) min; p = 0.540), median (1st-3rd q) estimated blood loss (EBL) (100 (100-150) vs. 100 (100-150) ml; p = 0.834), Clavien-Dindo (CD) ≥ 2 complications (3% vs. 4%; p = 0.498), and social continence at 3 months (73.7% vs. 74.7%; p = 0.353). In multiple analyses, no associations were found between surgical outcomes (PSM, length of PSM, operative time, EBL, length of catheterization, length of hospital stay, social continence at three months after surgery, and CD ≥ 2 complications) and the robotic platform. Conclusions: Our findings demonstrate that HugoTM RAS enables surgeons to safely and effectively transfer the level of proficiency they reached during their previous experience with the daVinci systems.

Robot-Assisted Radical Prostatectomy Performed with the Novel Hugo™ RAS System: A Systematic Review and Pooled Analysis of Surgical, Oncological, and Functional Outcomes.

Background/Objectives: to assess surgical, oncological, and functional outcomes of robot-assisted radical prostatectomy (RARP) performed using the novel Hugo™ RAS system. Methods: A systematic review was conducted following the PRISMA guidelines, using PubMed, Web of Science, Scopus, and Embase databases. Eligible papers included studies involving adult males undergoing RARP with the Hugo™ RAS platform, with at least ten patients analyzed. The pooled analysis was performed using a random-effect model. Results: Quantitative analysis was conducted on 12 studies including 579 patients. The pooled median docking time, console time, and operative time were 11 min (95% CI 7.95-14.50; I2 = 98.4%, ten studies), 142 min (95% CI 119.74-164.68; I2 = 96.5%, seven studies), and 176 min (95% CI 148.33-203.76; I2 = 96.3%, seven studies), respectively. The pooled median estimated blood loss was 223 mL (95% CI 166.75-280.17; I2 = 96.5%, eleven studies). The pooled median length of hospital stay and time to catheter removal were 2.8 days (95% CI 1.67-3.89; I2 = 100%, ten studies) and 8.3 days (95% CI 5.53-11.09; I2 = 100%, eight studies), respectively. The pooled rate of postoperative CD ≥ 2 complications was 4.1% (95% CI 1-8.5; I2 = 63.6%, eleven studies). The pooled rate of positive surgical margins and undetectable postoperative PSA were 20% (95% CI 12.6-28.5; I2 = 71.5%, nine studies) and 94.2% (95% CI 87.7-98.6; I2 = 48.9%, three studies), respectively. At three months, a pooled rate of social continence of 81.9% (95% CI 73.8-88.9; I2 = 66.7%, seven studies) was found. Erectile function at six months was 31% in one study. Conclusions: despite the preliminary nature of the evidence, this systematic review and pooled analysis underscores the feasibility, safety, and reproducibility of the Hugo™ RAS system in the context of RARP.

Robot-Assisted Radical Prostatectomy Performed with the Novel Surgical Robotic Platform Hugo™ RAS: Monocentric First Series of 132 Cases Reporting Surgical, and Early Functional and Oncological Outcomes at a Tertiary Referral Robotic Center.

BACKGROUND: Robotic-assisted surgery is the gold standard for performing radical prostatectomy (RARP), with new robotic devices such as HugoTM RAS gaining prominence worldwide. OBJECTIVE: We report the surgical, perioperative, and early postoperative outcomes of RARP using HugoTM RAS. DESIGN, SETTING, AND PARTICIPANTS: Between April 2022 and October 2023, we performed 132 procedures using the Montsouris technique with a four-robotic-arm configuration in patients with biopsy-proven prostate cancer (PCa). OUTCOME MEASURES: We collected intraoperative and perioperative data during hospitalization, along with follow-up data at predefined postoperative intervals of 3 and 6 months. RESULTS AND LIMITATIONS: Lymphadenectomy was performed in 25 procedures, with a bilateral nerve-sparing technique in 33 and a monolateral nerve-sparing technique in 33 cases. The mean total surgery time was 242 (±57) min, the mean console time was 124 (±48) min, and the mean docking time was 10 (±2) min. We identified 17 system errors related to robotic arm failures, 9 robotic instrument breakdowns, and 8 significant conflicts between robotic arms. One post-operative complication was classified as Clavien-Dindo 3b. None of the adverse events, whether singular or combined, increased the operative time. Positive margins (pR1) were found in 54 (40.9%) histological specimens, 37 (28.0%) of which were clinically significant. At 3 and 6 months post-surgery, the PSA levels were undetectable in 94.6% and 92.1% of patients, respectively. Social urinary continence was regained in 86% after 6 months. Limitations of our study include its observational monocentric case-series design and the short follow-up data for functional and oncological outcomes. CONCLUSIONS: Our initial experience highlights the reliability of the HugoTM RAS system in performing RARP. Additionally, we also list problems and solutions found in our daily work.

Assessing Trifecta and Pentafecta Success Rates between Robot-Assisted vs. Open Radical Cystectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to evaluate the surgical and oncological outcomes of robot-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) using trifecta and pentafecta parameters. METHODS: The clinical data of 41 patients who underwent RARC between 2018 and 2022 were prospectively collected and retrospectively compared to those of 330 patients undergoing ORC using 1:1 propensity score matching. Trifecta was defined as simultaneous negative surgical margins (SMs), a lymph node (LN) yield ≥ 16, and the absence of major complications (Clavien-Dindo grade III-V) within 90 days postoperatively. Pentafecta additionally included a 12-month recurrence-free rate and a time between the transurethral resection of a bladder tumor (TURBT) and radical cystectomy (RC) ≤ 3 months. The continuous variables were compared using the Mann-Whitney U test, and the categorical variables were analyzed using the chi-squared test. RESULTS: No statistically significant differences in trifecta and pentafecta success rates were observed between the RARC and ORC cohorts after propensity score matching. However, the RARC group exhibited significantly reduced blood loss (RARC: 317 mL vs. ORC: 525 mL, p = 0.01). CONCLUSIONS: RARC offers distinct advantages over ORC in terms of reduced blood loss, while trifecta and pentafecta success rates do not differ significantly between the two surgical approaches.

Simultaneous surgical management of renal cancer with atrial thrombotic extension and severe chronic coronary artery disease: a case report.

BACKGROUND: Renal cell carcinoma accounts for 2-3% of all malignant cancers in adults and is characterized by the potential development of venous tumor thrombus. CASE PRESENTATION: We present a rare case of a 62-year-old Caucasian man who arrived in the emergency department for monosymptomatic hematuria. Further investigation revealed a right renal cell carcinoma with 16 cm intravascular extension through the renal vein into the inferior vena cava and right atrium associated with significant coronary artery disease based on the computed tomography scan and coronary angiography. To the best of our knowledge, after an extensive literature review, only one similar case has been reported with involvement of the contralateral kidney. Therefore, there are no applicable management recommendations. After performing coronary artery bypass graft surgery, we proceeded with an open right radical nephrectomy and inferior vena cava and right atrium thrombectomy under cardiopulmonary bypass and while the patient's heart was still beating. The postoperative course went without complications, and the patient was discharged from the hospital on the 10th postoperative day. CONCLUSIONS: Radical nephrectomy and thrombectomy with reconstruction of the inferior vena cava combined with coronary artery bypass graft can be performed safely and effectively in selected patients with renal cell carcinoma and significant coronary artery disease. Multidisciplinary teamwork and careful patient selection are essential for optimal outcomes.

Germline mutations in prostate cancer: a systematic review of the evidence for personalized medicine.

BACKGROUND: The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5-15%. METHODS: A systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords "prostate cancer", "germline mutations", "family history", and "inheritance" was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: The search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer. DISCUSSION: Emerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.

Purely Off-Clamp Partial Nephrectomy: Robotic Approach Better than Open Using a Pentafecta Outcome with Propensity Score Matching.

Partial nephrectomy (PN) is the gold standard treatment for localized renal masses. Robot-assisted PN (RAPN) has overcome laparoscopy's technical limitations, greatly expanding the indications of minimally invasive PN, which is dominated by renal artery clamping in almost all published series. We compared off-clamp RAPN (OFFC-RAPN) with the open approach (OFFC-OPN) using propensity score (PS) matching. A favourable pentafecta outcome was defined as a combination of no positive surgical margins (PSM), no complications of Clavien−Dindo (CD) grade ≥ 3, post-operative eGFR loss <10%, length of hospital stay (LOS) ≤ 5 days and estimated blood loss (EBL) < 200 mL. A total of 340 consecutive patients were included. The PS-matched cohort included 142 patients: 71 matched pairs well-balanced for all covariates. The OFFC-RAPN group showed significantly shorter operative time (149.8 vs. 173.9 min, p = 0.003), lower EBL (182.1 vs. 329.3 mL, p = 0.001), and shorter LOS (5.8 vs. 6.9 days, p = 0.02), with a higher proportion of patients with LOS ≤ 5 days (57.7% vs. 23.9%, p < 0.001). No significant differences were found for PSM rate (2.8% vs. 8.4%, p = 0.27), CD > 2 complication rate (4.2% vs. 2.8%, p = 1.00) and mean ± SD eGFR change (−0.06 ± 0.3 vs. −0.8 ± 0.3, p = 0.5). Pentafecta was achieved in 56.3% and 21.1% in the OFFC-RAPN and OFFC-OPN series, respectively (p < 0.0001). On multivariable analysis, surgical approach and BMI proved to be independent predictors of achieving pentafecta. After adjusting for potential treatment selection bias, OFFC-RAPN outperformed OFFC-OPN for important peri-operative outcomes, without compromising oncological and functional safety.

18F-Fluoroethylcholine PET/CT Radiomic Analysis for Newly Diagnosed Prostate Cancer Patients: A Monocentric Study.

AIM: The aim of this study is to assess whether there are some correlations between radiomics and baseline clinical-biological data of prostate cancer (PC) patients using Fluorine-18 Fluoroethylcholine (18F-FECh) PET/CT. METHODS: Digital rectal examination results (DRE), Prostate-Specific Antigen (PSA) serum levels, and bioptical-Gleason Score (GS) were retrospectively collected in newly diagnosed PC patients and considered as outcomes of PC. Thereafter, Volumes of interest (VOI) encompassing the prostate of each patient were drawn to extract conventional and radiomic PET features. Radiomic bivariate models were set up using the most statistically relevant features and then trained/tested with a cross-fold validation test. The best bivariate models were expressed by mean and standard deviation to the normal area under the receiver operating characteristic curves (mAUC, sdAUC). RESULTS: Semiquantitative and radiomic analyses were performed on 67 consecutive patients. tSUVmean and tSkewness were significant DRE predictors at univariate analysis (OR 1.52 [1.01; 2.29], p = 0.047; OR 0.21 [0.07; 0.65], p = 0.007, respectively); moreover, tKurtosis was an independent DRE predictor at multivariate analysis (OR 0.64 [0.42; 0.96], p = 0.03) Among the most relevant bivariate models, szm_2.5D.z.entr + cm.clust.tend was a predictor of PSA levels (mAUC 0.83 ± 0.19); stat.kurt + stat.entropy predicted DRE (mAUC 0.79 ± 0.10); cm.info.corr.1 + szm_2.5D.szhge predicted GS (mAUC 0.78 ± 0.16). CONCLUSIONS: tSUVmean, tSkewness, and tKurtosis were predictors of DRE results only, while none of the PET parameters predicted PSA or GS significantly; 18F-FECh PET/CT radiomic models should be tested in larger cohort studies of newly diagnosed PC patients.

The new surgical robotic platform HUGOTM RAS: System description and docking settings for robot-assisted radical prostatectomy.

BACKGROUND: To date, robotic surgery in urology is well established all over the world. The newest platform on the market is the HUGO™ RAS system, developed by Medtronic. In this paper we provide a brief description of the system and describe our system set-up and surgical approach with this new platform in our initial experience of robotic radical prostatectomy (RARP) series. MATERIALS AND METHODS: After an official training, seven consecutive patients affected by localized prostate cancer underwent RARP with HUGOTM RAS system at our Institution. A description of our surgical approach and docking setup is provided. Docking and console times were reported for all precedures together with main suggestions to facilitate the use of this new system at the beginning of the experience. RESULTS: Our operating room setup has shown to be safe, effective, and easy replicable. During our series, operative times appeared to be easy reproducible and comparable to those obtained with daVinci system. No major system faults and conflicts between robotic arms were observed after the first procedure. CONCLUSIONS: Our surgical approach and system configuration for performing RARP with the new HUGO™ RAS system appears to be safe, efficient and easy reproducible.

A multi-surgeon learning curve analysis of overall and site-specific positive surgical margins after RARP and implications for training.

Robot-assisted radical prostatectomy (RARP) is the most adopted treatment for localized prostate cancer. The aim of this study was to explore the learning curves (LC) for overall and site-specific positive surgical margins (PSM) occurrence after RARP of multiple surgeons within a step-structured mentor-initiated training program. The study included consecutive patients undergoing RARP between January 2013 and March 2020, by three surgeons: a mentor and his two trainees. Prospectively collected patients' data were retrospectively analyzed. The cumulative summation (CUSUM) method was used to generate the LCs, with turning points indicating the number of cases to reach proficiency levels. Furthermore, the association between PSM and surgical experience was evaluated, adjusting for case mix. A total of 761 consecutive patients were included, 370 treated by the Mentor surgeon, 247 and 144 treated, respectively, by the two Trainees. Mentor and Trainees had similar PSM rates (31.6% vs 28.0% vs 31.3%, p = 0.6). CUSUM charts showed different LC shapes for different PSM locations (postero-lateral, bladder neck, apex, and multifocal/> 3 mm). Surgical experience was significantly associated with overall, postero-lateral, and multifocal/> 3 mm PSMs, in the Mentor series only. Trainees reached their turning points after far fewer cases then the Mentor, both for overall (12 and 31 vs 153), postero-lateral (24 and 30 vs 120), and multifocal/> 3 mm PSMs (9 and 31 vs 153). The achievement of stable SM proficiency takes involved different LCs depending on the prostatic location being considered. Monitoring site-specific LC can indicate the surgical steps for which there may be still room for further technical refinements, even when an apparent proficiency status seems achieved.

Male sling placement for post-prostatectomy incontinence can involve a lengthy learning curve: A multi-outcome assessment via cumulative sum failure analysis.

PURPOSES: Little research exists on potential learning curve for male sling procedures. We aimed to perform a learning curve analysis of a single surgeon's experience of sling placement evaluating multiple outcomes and using the cumulative sum failure methodology. METHODS: The study included 65 consecutive patients that underwent implantation of a fixed transobturator sling (TiLOOP Male) for post-radical prostatectomy stress incontinence at our institution from January 2013 to December 2018. Dichotomous outcomes evaluated with cumulative sum failure analysis included 12-months continence defined based on Patient Global Impression of Improvement (PGI-I) questionnaire (primary outcome), 24 h pad test and, 24 h pad use, operative time (⩽/>60 min), and complications (yes/no). Univariate and multivariate logistic regression analyses were performed to evaluate the association of the procedures' chronological sequence number with the outcomes. RESULTS: Cumulative sum failure curves revealed a clear and lengthy learning curve effect for most of subjective and quantitative continence outcomes and for operative time. For the primary outcome (at least much improved at PGI-I), 62 procedures were required to overcome the learning curve. Accordingly, multivariate analyses showed that the sequence number was statistically significant for predicting failures based on PGI-I (adjusted OR 0.95; 95% CI: 0.91-0.99; p = 0.02), objective outcomes, and operative time. CONCLUSIONS: An evident and lengthy learning curve was observed in our series of male sling placement to achieve the end level of proficiency, independently from case-mix. Individualized structured training on male sling surgery will benefit patients treated in the initial surgeon's experience. Surgical experience should be considered when reporting studies on male slings.

The bladder epicheck test and cytology in the follow-up of patients with non-muscle-invasive high grade bladder carcinoma.

BACKGROUND: The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection of a bladder tumor consists of adjuvant intravesical therapy and strict and long surveillance with urine cytology and cystoscopy. The Bladder EpiCheck test (Nucleix Ltd) (BE) is a newly developed urinary markers based on DNA methylation changes in a panel of 15 genomic biomarkers, with a promising performance in term of non-invasive NMIBC detection. METHODS: In this study we prospectively enrolled 151 consecutive patients with high grade NMIBC, treated with intravesical BCG and mitomycin C therapy and evaluated during the follow-up by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. The Bladder EpiCheck test was performed at the same time of urine cytology in voided specimen. In all cases with positive cytology the diagnosis was confirmed by histology and a diagnosis was made according to the 2017 tumor, node, metastasis (TNM) classification and graded using both the 1973 and the 2004 World Health Organization (WHO) classifications. RESULTS: At three months of follow-up, we reported similar overall specificity rates for BE and urine cytology (85,1% vs 86,3%). In the group of patients with carcinoma in situ (CIS), we found the same specificity for BE and urine cytology (81,4%), while in the groups of patients with papillary high grade NMIBC, the specificity of BE was higher compared to cytology (96,3% vs 90,4%). The sensitivity of BE was always higher compared to cytology during all the follow-up both for papillary NMIBC and CIS. CONCLUSION: In the early follow-up of NMIBC the EpiCheck test might replace urinary cytology.

Multiparametric magnetic resonance imaging of the prostate: Lights and shadows.

Prostate cancer is the second most commonly diagnosed cancer in man. Since the first MRI was performed, enormous progress has been made in diagnosis, treatment, and follow up of PCa, mainly due to multiparametric prostatic MRI (mpMRI). Although mpMRI has become the best imaging tool for identifying PCa, some limitations still exist. Prostate imaging with mpMRI is, to date, the best way to locate suspicious lesions to trigger prostate biopsy, plan active surveillance, or definitive treatment. In case of relapse, mpMRI can help detect local disease and provide specific management. It is well known that there is a subset of patients in whom mpMRI fails to depict csPCa. These missed significant cancers demand great attention. Prostate mpMRI quality depends on several factors related to equipment (including equipment vendor, magnet field and gradient strength, coil set used, software and hardware levels, sequence parameter choices), patient (medications, body habitus, motion, metal implants, rectal gas), and most importantly the radiologic interpretation of images (learning curve effects, subjectivity of observations, interobserver variations, and reporting styles). Inter-reader variability represents a huge current limitation of this method. Therefore, mpMRI remains the best imaging tool available to detect PCa, guiding diagnosis, treatment, and follow up while inter-reader variability represents the best limitation. Radiomics can help identifying imaging biomarkers to help radiologist in detecting significant PCa, reducing examination times, and costs.

Lifestyle in urology: Benign diseases.

Modifiable lifestyle-related risk factors are the object of increasing attention, with a view to primary and tertiary prevention, to limit the onset and development of diseases.Also in the urological field there is accumulating evidence of the relationship between urological diseases and lifestyle-related risk factors that can influence their incidence and prognosis. Risk factors such as nutrition, physical activity, sexual habits, tobacco smoking, or alcohol consumption can be modified to limit morbidity and reduce the social impact and the burdensome costs associated with diagnosis and treatment.This review synthesizes the current clinical evidence available on this topic, trying to satisfy the need for a summary on the relationships between the most important lifestyle factors and the main benign urological diseases, focusing on benign prostatic hyperplasia (BPH), infections urinary tract (UTI), urinary incontinence (UI), stones, erectile dysfunction, and male infertility.

Bladder cancer in the time of machine learning: Intelligent tools for diagnosis and management.

Machine learning (ML) is the subfield of artificial intelligence (AI), born from the marriage between statistics and computer science, with the unique purpose of building prediction algorithms able to improve their performances by automatically learning from massive data sets. The availability of ever-growing computational power and highly evolved pattern recognition software has led to the spread of ML-based systems able to perform complex tasks in bioinformatics, medical imaging, and diagnostics. These intelligent tools could be the answer to the unmet need for non-invasive and patient-tailored instruments for the diagnosis and management of bladder cancer (BC), which are still based on old technologies and unchanged nomograms. We reviewed the most significant evidence on ML in the diagnosis, prognosis, and management of bladder cancer, to find out if these intelligent technologies are ready to be introduced into the daily clinical practice of the urologist.

Methylation study of the Paris system for reporting urinary (TPS) categories.

AIMS: Bladder EpiCheck is one of several urinary tests studied to identify bladder tumours and analyses 15 methylation biomarkers determining bladder cancer presence on the basis of methylation profile. METHODS: 374 patients diagnosed with high-grade non-muscle invasive bladder cancer were treated and followed for 1 year with voided urine cytology and white-light cystoscopy and biopsies according to European Association of Urology Guidelines. 268 cases were diagnosed with high-grade papillary carcinoma, while 106 cases were carcinoma in situ. Bladder EpiCheck test was performed together with cytology in all cases. RESULTS: Comparing cytological categories of negative for high-grade urothelial carcinoma (NHGUC) and atypical urothelial cells (AUCs), we found that an EpiScore <60 correlates with NHGUC (p=0.0003, Fisher's exact test), while comparing AUC and suspicious for high-grade urothelial carcinoma (SHGUC) or SHGUC and high-grade urothelial carcinoma (HGUC) categories, an EpiScore ≥60 correlates with SHGUC and HGUC, respectively (p=0.0031 and p=0.0027, Fisher's exact test). In each TPS category, we found that sensitivity, specificity, Positive Predicitve Value (PPV) and Negative Predictive Value (NPV) of the Bladder EpiCheck test in HGUC category were higher than those observed in SHGUC group (sensitivity=98%, specificity=100%, NPV=85.7%, PPV=100% vs sensitivity=86.6%, specificity=52.3%, NPV=84.6%, PPV=56.5%). CONCLUSIONS: Analysing methylation study results, we demonstrated that different TPS cytological categories also carry a distinct molecular signature. Moreover, our results confirm that cytological categories SHGUC and HGUC are different entities also from a molecular point of view and should continue to represent distinct groups in TPS.

Correction to: PD-L1 expression in bladder primary in situ urothelial carcinoma: evaluation in BCG-unresponsive patients and BCG responders.

This correction is being done to update the right surname of first name of authors of this manuscript. This does not change the results or the views presented in this manuscript.

PD-L1 expression in bladder primary in situ urothelial carcinoma: evaluation in BCG-unresponsive patients and BCG responders.

Carcinoma in situ (CIS) is believed to be a precursor of muscle-invasive carcinomas that may arise from these flat high-grade, superficial urothelial lesions. CIS accounts for approximately 10% of all bladder tumors. Therapeutic options for urothelial CIS are limited, and in order to inhibit disease progression and recurrence, current guidelines recommend transurethral resection (TURBT) followed by intravesical administration of Bacillus of Calmette-Guerin (BCG). Approximately 30-40% of patients fail the BCG therapy with recurrence and progression of disease. In the present study, we examined the expression of PD-L1 both in neoplastic epithelial cells and in stromal inflammatory cells in patients with diagnosis of CIS primary responders and not responders to BCG therapy, in order to verify if the PD-L1 expression could identify patients resistant to BCG treatment. Moreover, we analyzed on the same cases the immunoreactivities of anti-PD-L1 MoAbs such as SP263, C23, and SP142. Our results have showed that PD-L1 expression in tumor cells and in immune cell compartment is higher in BCG-unresponsive group than in BCG responders, but only the PD-L1 22C3 expression in tumor cells seems to be associated with recurrence of disease (p = 0.035; OR 0.1204; CI 95% from 0.0147 to 1.023). Hence, our data suggest that the PD-L1 22C3 expression could help to identify CIS that fail the BCG therapy, supporting the hypothesis that enhanced levels of intratumoral PD-L1 22C3 expressed by the tumor cells may explain the failure of BCG immunotherapy.

The occult urothelial cancer.

Transitional cell carcinoma (TCC) is the tumor that most frequently affects the urinary tract. The most common location is in the bladder; the diagnosis, as the follow-up, is based on urine cytology, endoscopic, and radiological examinations. Urinary cytology is an important non invasive tool used in the diagnosis and follow-up of patients with TCC. A positive urine cytology result is highly predictive of the presence of TCC, even in the presence of normal cystoscopy, because malignant cells may appear in the urine long time before any cystoscopically visible lesion becomes apparent. The presence of a positive urinary cytology, in the absence of clinical or endoscopic evidence of a TCC, can identify an occult urothelial cancer, located in any site of the urinary tract (upper urinary tract, bladder, prostatic urethra). Most of the urothelial tumors of the renal pelvis and ureters are diagnosed by radiological examinations, but we can observe a high rate of false negatives. In order to improve the diagnostic role of urinary cytology and other conventional examinations, numerous molecular markers have been identified; however, the real clinical application remains unclear. Photodynamic diagnosis and narrow band imaging (NBI) cystoscopy increase the diagnostic accuracy of endoscopic examinations in the presence of lesions not easily detectable. The aim of this review is to analyze the current diagnostic standards in the presence of occult urothelial cancer.