Vesical Imaging-Reporting and Data System use predicting the outcome of neoadjuvant pembrolizumab in muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the predictive capability of the pre- and post-pembrolizumab Vesical Imaging-Reporting and Data System (VI-RADS) to identify ypT0N0 or ypT≤1N0 response in muscle-invasive bladder cancer (MIBC) within the PURE-01 trial (ClinicalTrials.gov identifier: NCT02736266). PATIENTS AND METHODS: Patients were staged with bladder multiparametric magnetic resonance imaging (mpMRI) before and after treatment (three cycles of pembrolizumab) prior to radical cystectomy (RC). Logistic regression models were used to analyse the pre- and post- pembrolizumab VI-RADS against ypT≤1N0 and ypT0N0 response. The VI-RADS scores were dichotomised between 0 and 3 (0 = no evidence of disease) and 4-5. Event-free survival (EFS) and overall survival (OS) analyses were performed. Comprehensive genomic profiling and transcriptome-wide expression profiling data were matched with the VI-RADS scores. RESULTS: In total, 110 patients underwent centrally reviewed scans (N = 220 mpMRI), treated between February 2017 and July 2020. Both pre- and post-pembrolizumab VI-RADS 0-3 scores were the only significant covariates that predicted the ypT≤1N0 endpoint in multivariable analyses, and the strongest effect was seen with post-pembrolizumab VI-RADS 0-3 predicting the ypT≤1N0 response (P < 0.001). The area under the curve for this model was 0.90. Post-pembrolizumab VI-RADS 0-3 also predicted a longer EFS (P < 0.001) and OS (P = 0.044). The scores of several gene signatures from baseline tumours differed between the pre-pembrolizumab VI-RADS 0-3 and 4-5 categories. CONCLUSION: Post-pembrolizumab VI-RADS scores are strongly associated with pathological downstaging and survival. VI-RADS scores were also characterised by distinct biomarker features. These results indicate that the VI-RADS is emerging as an important tool for designing next-generation trials for MIBC.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

OBJECTIVE: To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). MATERIALS AND METHODS: This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. RESULTS: At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. CONCLUSIONS: In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Peri- and post-operative outcomes of robot-assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high-volume referral center.

PURPOSE: No studies relied on a standardized methodology to collect postoperative complications after robot-assisted radical cystectomy (RARC). The aim of our study was to evaluate peri- and post-operative outcomes of patients undergoing RARC adhering to the European Association of Urology (EAU) recommendations for reporting surgical outcomes and using a long postoperative follow-up. MATERIALS AND METHODS: 246 patients who underwent RARC with intracorporal urinary diversion at a single tertiary referral center with a postoperative follow-up ≥ 1 year for survivors. Postoperative outcomes were collected prospectively by interviews done by medical doctors. Complications were scored using the Clavien-Dindo classification (CD), grouped by type and severity (severe: CD score ≥ 3). We described peri- and post-operative outcomes and complication chronological distribution. RESULTS: Overall, 16 (6.5%) and 225 patients (91%) experienced intraoperative and postoperative complications, respectively. Moreover, 139 (57%) experienced severe complications. The most common any-grade and severe complications were infectious (72%) and genitourinary (35%), respectively. Overall, 52% of complications (358/682) occurred within 10 days from surgery, and 51% of severe complications (106/207) occurred within 35 days. However, 13% of complications (90/682) and 28% of severe complications (59/207) occurred 3 months after surgery. The earliest complications were fever of unknown origins and paralytic ileus (median time-to-complication [mTTC]: 4 days), the latest complications were urinary tract infection (mTTC: 40 days) and hydronephrosis/ureteral obstruction (mTTC: 70 days). CONCLUSIONS: The rate of postoperative complications after RARC is > 90% when a standardized collection method and a long follow-up is implemented. These results should be used to identify potential areas of improvement and for preoperative patient counseling.

Human metabolism of four synthetic benzimidazole opioids: isotonitazene, metonitazene, etodesnitazene, and metodesnitazene.

Following isotonitazene scheduling in 2019, the availability of alternative 2-benzylbenzimidazole opioids (nitazenes) on the global drug market increased, resulting in many fatalities worldwide. Nitazenes are potent µ-opioid receptor agonists with strong narcotic/analgesic effects, and their concentrations in biological matrices are low, making the detection of metabolite biomarkers of consumption crucial to document use in clinical and forensic settings. However, there is little to no data on the metabolism of the most recently available nitazenes, especially desnitro-analogues. The aim of the research was to assess isotonitazene, metonitazene, etodesnitazene, and metodesnitazene human metabolism and identify specific metabolite biomarkers of consumption. The four analogues were incubated with 10-donor-pooled human hepatocytes, and the incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry and data mining with Compound Discoverer (Thermo Scientific); the analysis was supported by in silico metabolite predictions with GLORYx open-access software. Metabolites were identified in postmortem blood and/or urine samples from two metonitazene-positive and three etodesnitazene-positive cases following the same workflow, with and without glucuronide hydrolysis in urine, to confirm in vitro results. Twelve, nine, twenty-two, and ten metabolites were identified for isotonitazene, metonitazene, etodesnitazene, and metodesnitazene, respectively. The main transformations were N-deethylation at the N,N-diethylethanamine side chain, O-dealkylation, and further O-glucuronidation. In vitro and autopsy results were consistent, demonstrating the efficacy of the 10-donor-pooled human hepatocyte model to predict human metabolism. We suggest the parent and the corresponding O-dealkyl- and N-deethyl-O-dealkyl metabolites as biomarkers of exposure in urine after glucuronide hydrolysis, and the corresponding N-deethyl metabolite as additional biomarker in blood.

Optimizing decision-making after ventral onlay buccal mucosa graft urethroplasty failure.

OBJECTIVES: To evaluate factors predicting recurrence after treatment and to assess the best rescue option for patients failing buccal mucosa graft (BMG) urethroplasty. MATERIALS AND METHODS: We evaluated the data from 575 patients treated with ventral onlay BMG urethroplasty. Multivariable Cox regression analysis was performed to identify predictors of BMG urethroplasty failure, and their effect on failure risk was estimated using the Kaplan-Meier method and compared using log-rank tests. Then, for those patients who underwent a rescue treatment, namely, direct visual internal urethrotomy (DVIU) vs open urethroplasty, we assessed the probability of success after retreatment using the Kaplan-Meier method and regression tree analyses. RESULTS: On multivariable Cox regression analysis, only stricture length ≥5 cm (hazard ratio 3.46, 95% confidence interval 1.50-7.94; P = 0.003) was a predictor of failure. A total of 103 patients had at least one re-intervention. Notably, 12-month success rates after first rescue DVIU, second rescue DVIU, third rescue DVIU, and fourth rescue DVIU were 66.3%, 62.5%, 37.5% and 25%, respectively. Conversely, for those patients who underwent open urethroplasty retreatment, success rates at 12 months were 83.3%, 79%, 92.3% and 75% after BMG ventral onlay, first rescue DVIU, second rescue DVIU and third rescue DVIU, respectively. These data were confirmed in regression tree analyses. CONCLUSION: Ventral BMG urethroplasty fails in approximately one out of five patients. Despite DVIU as a rescue treatment being a good option, its success rate becomes lower as the number of DVIU treatments performed increases. Conversely, open urethroplasty improves patient outcomes in almost three out of four patients, even in the case of previous failed DVIU treatments for stricture recurrence.

Risks and benefits of partial nephrectomy performed with limited or with zero ischaemia time.

OBJECTIVE: To test the hypothesis that longer warm ischaemia time (WIT) might have a marginal impact on renal functional outcomes and might, in fact, reduce haemorrhagic risk intra-operatively. PATIENTS AND METHODS: Data from 1140 patients treated with elective partial nephrectomy (PN) for a cT1-2 cN0 cM0 renal mass were prospectively collected. WIT was defined as the duration of clamping of the main renal artery with no refrigeration and was tested as a continuous variable. The primary outcome of the study was evaluation of the effect of WIT on renal function (estimated glomerular filtration rate [eGFR]) postoperatively, at 6 months and in the long term (measured between 1 and 5 years after surgery). The secondary outcome of the study was haemorrhagic risk, defined as estimated blood loss (EBL) or peri-operative transfusions. Multivariable linear, logistic and Cox regression analyses, accounting for age, Charlson comorbidity index, clinical size, preoperative eGFR and year of surgery, were used and the potential nonlinear relationship between WIT and the study outcomes was modelled using restricted cubic splines. RESULTS: A total of 863 patients (76%) underwent PN with WIT and 277 (24%) without. The baseline median eGFR was 87.3 (68.8-99.2) mL/min/1.73m2 for the on-clamp population and 80.6 (63.2-95.2) mL/min/1.73m2  for the off-clamp population. The median duration of WIT was 17 (13-21) min. At multivariable analyses predicting renal function, longer WIT was associated with decreased postoperative eGFR (estimate: -0.21, 95% confidence interval [CI] -0.31; -0.11 [P < 0.001]). Conversely, no association between WIT and eGFR was recorded at 6-month or long-term follow-up (all P > 0.8). At multivariable analyses predicting haemorrhagic risk, clampless resection with no ischaemia time and PN with short WIT was associated with an increased EBL (estimate: -21.56, 95% CI -28.33; -14.79 [P < 0.001]) and peri-operative transfusion rate (estimate: -0.009, 95% CI -0.01; -0.003 [P = 0.002]). No association between WIT and positive surgical margin status was recorded (all P = 0.1). CONCLUSION: Patients and clinicians should be aware that performing PN with very limited or even with zero WIT might increase bleeding and the need for peri-operative transfusion while not improving long-term renal function outcomes.

Novel single-stage preputial spiral graft for panurethral stricture: a step-by-step description of the technique.

PURPOSE: To report the 12-month results of a novel urethroplasty technique relying on a spiral preputial graft for panurethral stricture disease. MATERIALS AND METHODS: Twenty consecutive patients were treated between May and October 2021 at our center. A spiral preputial mucocutaneous graft is a foreskin-based graft, developed from a 5-cm-wide preputial skin, which is harvested using a helicoidal shape and can reach up to 20 cm in length. Stricture characteristics were assessed through preoperative retrograde and voiding cystourethrogram and maximum uroflowmetry data (Qmax). Complications were collected up to 30 days after surgery and graded using the Clavien-Dindo (C-D) classification. The patients were followed up to 12 months. RESULTS: Preoperative median Qmax was 6.5 ml/s [interquartile range (IQR): 4.0-8.7]. After a median follow-up of 12 months (IQR 12-13), six patients experienced at least one complication. Of them, two patients had grade 2 C-D complications, while only one developed a grade 3a C-D complication. The median postoperative Qmax was 16 ml/s (IQR: 13-18). Only one patient had early urethral stricture recurrence treated with dilatation after catheter removal. At one-year follow-up, no other patients had urethral stricture recurrence with an overall median Qmax of 15.1 ml/s (IQR 13.5-16.4). CONCLUSIONS: Our novel single-stage spiral preputial graft urethroplasty for panurethral stricture treatment appears to be safe and could be used as a valid alternative to two-stage procedures or even to single-stage buccal mucosa graft augmentation.

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.

The importance of second-look ureteroscopy implementation in the conservative management of upper tract urothelial carcinoma.

PURPOSE: The purpose of the study was to evaluate the effect of second-look ureteroscopy (SU) in the endoscopic operative work-up of patients with upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients with UTUC who underwent SU between 2016 and 2021 were included. Cancer detection rate (CDR) at SU was defined as endoscopic visualization of tumor. The effect of SU on recurrence-free survival (RFS), radical nephroureterectomy-free survival (RNU-FS), bladder cancer-free survival (BC-FS), and cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Multivariate logistic regression analysis (MLR) assessed predictors of negative SU. Finally, we evaluated the effect of SU timing on oncological outcomes, classifying SUs as "early" (≤ 8 weeks) and "late" (> 8 weeks). RESULTS: Overall, 85 patients underwent SU. The CDR at SU was 44.7%. After a median follow-up was 35 (IQR: 15-56) months, patients with positive SU had a higher rate of UTUC recurrence (47.4% vs 19.1%, p = 0.01) and were more frequently radically treated (34.2% vs 8.5%, p = 0.007). Patients with high-grade disease (hazard ratio [HR]: 3.14, 95% CI 1.18-8.31; p = 0.02) had a higher risk of UTUC recurrence, while high-grade tumor (HR: 3.87, 95%CI 1.08-13.77; p = 0.04) and positive SU (HR: 4.56, 95%CI 1.05-22.81; p = 0.04) were both predictors of RNU. Low-grade tumors [odds ratio (OR): 5.26, 95%CI 1.81-17.07, p = 0.003] and tumor dimension < 20 mm (OR: 5.69, 95%CI 1.48-28.31, p = 0.01) were predictors of negative SU. Finally, no significant difference emerged regarding UTUC recurrence, RNU, BC-FS, and CSM between early vs. late SUs (all p > 0.05). CONCLUSIONS: SU may help in identifying patients with UTUC experiencing an early recurrence after conservative treatment. Patients with low-grade and small tumors are those in which SU could be safely postponed after 8 weeks.

A new machine-learning model to predict long-term renal function impairment after minimally invasive partial nephrectomy: the Fundació Puigvert predictive model.

PURPOSE: To provide a new model to predict long-term renal function impairment after partial nephrectomy (PN). METHODS: Data of consecutive patients who underwent minimally invasive PN from 2005 to 2022 were analyzed. A minimum of 12 months of follow-up was required. We relied on a machine-learning algorithm, namely classification and regression tree (CART), to identify the predictors and associated clusters of chronic kidney disease (CKD) stage migration during follow-up. RESULTS: 568 patients underwent minimally invasive PN at our center. A total of 381 patients met our inclusion criteria. The median follow-up was 69 (IQR 38-99) months. A total of 103 (27%) patients experienced CKD stage migration at last follow-up. Progression of CKD stage after surgery, ACCI and baseline CKD stage were selected as the most informative risk factors to predict CKD progression, leading to the creation of four clusters. The progression of CKD stage rates for cluster #1 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI 1-4), #2 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI ≥ 5), #3 (no progression of CKD stage after surgery and baseline CKD stage 3-4-5) and #4 (progression of CKD stage after surgery) were 6.9%, 28.2%, 37.1%, and 69.6%, respectively. The c-index of the model was 0.75. CONCLUSION: We developed a new model to predict long-term renal function impairment after PN where the perioperative loss of renal function plays a pivotal role to predict lack of functional recovery. This model could help identify patients in whom functional follow-up should be intensified to minimize possible worsening factors of renal function.

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.

Neglected lymph nodal metastases in patients with renal cancer: when to extend the anatomical template of lymph node dissection during nephrectomy.

BACKGROUND: The role of lymph node dissection (LND) in patients with renal cell carcinoma (RCC) is still controversial. However, detecting lymph node invasion (LNI) is key due to prognostic implications and to identify patients who might benefit from adjuvant therapies such as adjuvant pembrolizumab. MATERIALS AND METHODS: Out of 796 patients, 261 (33%) received eLND, of whom 62 (8%) for suspicious lymph node (LN) metastases at preoperative staging (cN1). eLND was divided in 3 anatomical areas: (1) hilar, (2) side-specific (pre-/para-aortic or pre-/para-caval) and (3) inter-aorto-caval nodes. Overall maximum LN diameter was measured by a dedicated radiologist for each patient. Multivariable logistic regression models (MVA) were tested for the effect of maximum LN diameter in predicting the presence of nodal metastases outside the anatomical area of cN1. RESULTS: LNI was confirmed in 50% of cN1, whilst only 13 out of 199 cN0 patients were pN1 at final histology (6.5%; p < 0.001). In a per-patient analysis, of 62 cN1 patients, 24% vs. 18% vs. 8% harboured pN1 disease only inside vs. in-outside vs. only outside the suspicious anatomical field of cN1 at preoperative CT/MRI scan. At MVA, increasing diameter of suspicious LNs was independently associated with risk of finding positive LNs outside the suspicious anatomical field (OR 1.05, 95%CI 1.02-1.11; p = 0.02). CONCLUSIONS: Roughly 50% of cN1 patients undergoing eLND will harbour LN metastases, also outside the suspicious radiological area, and maximum LNs diameter at preoperative imaging correlates with such risk. Thus, an eLND might be justified in patients with large suspicious LN metastases, to better stage this patient population and to improve postoperative treatment management.

New technologies for nephron-sparing surgery in upper urinary tract cancers.

PURPOSE OF REVIEW: Nephron-sparing surgery (NSS) is the preferred treatment in patients with low-risk upper tract urothelial carcinoma (UTUC). Improving both instruments and topical chemotherapy regimens efficacy is crucial to achieve better outcomes. The purpose of this review is to summarize the most recent evidence on technological advances for the conservative management of UTUC with implications on diagnosis and treatment. RECENT FINDINGS: Novel diagnostic tools, lasers, and topical chemotherapy systems delivery have been implemented to optimize NSS outcomes for UTUC. SUMMARY: Photodynamic ureteroscopy has been reported to improve cancer detection rate as compared with conventional imaging or ureteroscopy, especially in case of carcinoma in situ . However, refinements in photosensitizer administration and dedicated instruments are needed. The armamentarium of lasers for UTUC ablation is composed of several devices with peculiar characteristics. Together with Ho:YAG and Tm:YAG lasers, the Thulium Fiber Laser (TFL) is gaining momentum in UTUC ablation. Strengths and weaknesses of each laser must be considered to maximize oncological and safety outcomes. Several novel endocavitary chemotherapy delivery systems have been tested to reduce tumor recurrence and progression after NSS. Administration of gel-based chemotherapeutic agents has been proven to be effective in humans; conversely, drug-eluting ureteral stent systems are still conceptual.

Bladder-sparing strategies in patients with clinically localized muscle-invasive bladder cancer.

PURPOSE OF REVIEW: Radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). In this context, bladder-sparing strategies (BSS) have been investigated as viable alternatives for patients who are unfit for radical cystectomy or aim to preserve their bladder without compromising oncological outcomes. This review aims to provide the most up-to-date evidence on BSSs as an alternative treatment for patients with MIBC. RECENT FINDINGS: Different studies have highlighted the long-term efficacy of trimodal therapy or chemoradiation protocols. However, due to the lack of randomized controlled trials, there is still a lack of high-level evidence on BSS efficacy as compared to radical cystectomy. Consequently, the adoption of these approaches is still limited. A possible turning point could be represented by the introduction of immunotherapy, as several studies are investigating the potential combination with chemoradiotherapy or radiotherapy alone. Patient selection, together with the implementation of new predictive biomarkers and imaging tools, may improve the efficacy of BSS in the near future. SUMMARY: Radical cystectomy with perioperative chemotherapy remains the gold standard treatment for MIBC patients. Nevertheless, BSS can be considered a viable option in selected patients who desire to preserve their bladder. Further evidence is needed to clearly state the role of BSS in MIBC.

Organ-sparing treatment for T1 and T2 penile cancer: an updated literature review.

PURPOSE OF REVIEW: Penile cancer (PeCa) is an orphan disease due to its rare incidence in high-income countries. Traditional surgical options for clinical T1-2 disease, including partial and total penectomy, can dramatically affect patient's quality of life and mental health status. In selected patients, organ-sparing surgery (OSS) has the potential to remove the primary tumor with comparable oncologic outcomes while maintaining penile length, sexual and urinary function. In this review, we aim to discuss the indications, advantages, and outcomes of various OSSs currently available for men diagnosed with PeCa seeking an organ-preserving option. RECENT FINDINGS: Patient survival largely depends on spotting and treating lymph node metastasis at an early stage. The required surgical and radiotherapy skill sets cannot be expected to be available in all centers. Consequently, patients should be referred to high-volume centers to receive the best available treatments for PeCa. SUMMARY: OSS should be used for small and localized PeCa (T1-T2) as an alternative to partial penectomy to preserve patient's quality of life while maintaining sexual and urinary function and penile aesthetics. Overall, there are different techniques that can be used with different response and recurrence rates. In case of tumor recurrence, partial penectomy or radical penectomy is feasible, without impacting overall survival.

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer-Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects.

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and-as much as possible-minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

Robot-assisted radical cystectomy and ileal conduit with HugoTM RAS system: feasibility, setting and perioperative outcomes.

INTRODUCTION: Robotic approach has shown its feasibility and safety with respect to open approach for radical cystectomy (1). The performances of HugoTM RAS system (Medtronic, Minneapolis, USA) have been demonstrated in several clinical scenarios (2-5). We report the feasibility and surgical settings of the first series of robot-assisted radical cystectomy (RARC) with intracorporeal ileal-conduit performed with HugoTM RAS system. METHODS: Two patients were submitted to RARC with ileal conduit at our institution. The trocar placement scheme and the operating room setting with docking angles of the four arms were already described (6). A 12-mm and a 5-mm trocar for the assistant were placed. In both cases, an ileal-conduit with a Wallace type-1 uretero-enteric derivation was performed intra-corporeally. RESULTS: The first patient was a 71-year-old male with a very-high risk non-muscle invasive bladder cancer(BC), and the second patient was a 64-year-old male with a diagnosis of T2 high-grade BC. Operative times were 360 and 420 minutes with a docking time of 12 and 9 minutes, respectively. No intraoperative complications occurred. The estimated blood loss was 200ml and 400ml, respectively. The second patient developed an ileus on postoperative day 4 (Clavien-Dindo grade 2). No positive surgical margins were recorded. No recurrence nor progression occurred during follow-up. CONCLUSION: RARC with intracorporeal ileal conduit urinary diversion is feasible with HugoTM RAS system. We provided insight into the surgical setting using this novel robotic platform to help new adopters to face this challenging procedure. These findings may help a wider distribution of robotic programs for BC treatment.

Advanced Squamous Cell Carcinomas of the Pelvic and Perineal Region: A Comprehensive Genomic Profiling Study.

BACKGROUND: Advanced pelvic squamous cell carcinoma (pSCC) is a broad category of cancers affecting different pelvic organs and usually featuring unfavorable clinical outcomes. Thus, we aimed to assess genomic differences among pSCC cases and learn whether pSCC could potentially benefit from targeted therapies and/or immunotherapy. MATERIALS AND METHODS: A total of 1917 advanced pSCCs, including penile (penSCC), male urethral (murthSCC), male anal (manSCC), female urethral (furthSCC), vulvar (vulSCC), cervical (crvSCC), female anal (fanSCC), and vaginal (vagSCC), underwent comprehensive genomic profiling (CGP). We used hybrid capture-based CGP to evaluate recurrent genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 95 loci. Programmed cell-death-ligand-1 (PD-L1) expression was determined by immunohistochemistry (IHC; Dako 22C3). RESULTS: PIK3CA was the most frequently identified potentially "actionable" GA (22%-43%), followed by mTOR pathway [PTEN (0%-18%), FBXW7 (7%-29%)], and cell-cycle GAs. DNA-damage response (DDR) GAs and receptor-tyrosine kinase (RTK) targeted options were uncommon. NOTCH1 GAs were present in >15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was >15% in manSCC, fanSCC, crvSCC, and vagSCC. PD-L1 high expression was >18% in all pSCC except urthSCC, manSCC, and vagSCC. HPV-16/18 detection was highest in manSCC, fanSCC, and crvSCC. CONCLUSION: Despite similar histology, pSCCs can differ in GAs and HPV status. Overall, PIK3CA is the most frequent potentially "targetable" GA followed by mTOR and cell cycle pathway. RTK and DDR GAs are rare in pSCC. Immunotherapy could be considered for pSCC management based on TMB and PD-L1 expression.

Pancreatic metastases after surgery for renal cell carcinoma: survival and pathways of progression.

PURPOSE: Metastatic ccRCC has peculiar tropism in the pancreas. We describe the characteristics and pathways of progression of patients with PM in a large multi-institutional consortium and compare them to patients with metastases from ccRCC at other sites. METHODS: Detailed clinical and histopathological data were collected. To account for differences in baseline characteristics between the two groups, IPTW was used to compare the two groups in terms of PFS and OS. RESULTS: Of the 182 patients, 33 (18%) had pancreatic, 94 (52%) pulmonary, 30 (16%) bone, 13 (7%) hepatic, and 12 (7%) brain metastases. Patients with PM had less aggressive ccRCC at baseline compared to those with progression at other sites in terms of tumour stage and grade. Median time from ccRCC surgery to PM was 8 (95%CI 5-10) vs. 1 year (95%CI 1-2) for progression to other sites (p < 0.001). Median IPTW-weighted time to second progression was 4.3 years (95%CI 2.4-not reached) for patients with PM vs 1.1 year (95%CI 0.8-2.3) for those with progression in other sites (p < 0.001). The most frequent second progression sites were pancreas (24%) and liver (15%) in patients with PM, while progression to the pancreas was rare (4%) in those with a different first progression site. Surgery alone (55%) or in combination with medical therapy (30%) was more frequent in the PM group than in other sites (p < 0.001). Median IPTW-OS time was longer for patients with PM [8.8 years (95%CI 6.5-not reached)] compared to those with first progression in other sites [2.8 years (95%CI 1.9-4.3), p < 0.001]. CONCLUSION: Pancreatic tropism is typical of ccRCC tumours with more indolent behaviour than those progressing to other sites. A long follow-up period is necessary to distinguish PM from ccRCC.

How to optimize the use of adjuvant pembrolizumab in renal cell carcinoma: which patients benefit the most?

PURPOSE: The KEYNOTE-564 trial showed improved disease-free survival (DFS) for patients with high-risk renal cell carcinoma (RCC) receiving adjuvant pembrolizumab as compared to placebo. However, if systematically administered to all high-risk patients, it might lead to the overtreatment in a non-negligible proportion of patient. Therefore, we aimed to determine the optimal candidate for adjuvant pembrolizumab. METHODS: Within a prospectively maintained database we selected patients who fulfilled the inclusion criteria of the KEYNOTE-564. We compared baseline characteristics and oncologic outcomes in this cohort with those of the placebo arm of the KEYNOTE-564. Regression tree analyses was used to generate a risk stratification tool to predict 1-year DFS after surgery. RESULTS: In the off-trial setting, patients had worse tumor characteristics then in the KEYNOTE-564 placebo arm, i.e. there were more pT4 (5.4 vs. 2.7%, p = 0.046) and pN1 (15 vs. 6.3%, p < 0.001) cases. Median DFS was 29 (95% CI 21-35) months as compared to value not reached in KEYNOTE-564 and 1-year DFS was 64.2% (95% CI 59.6-69.2) as compared to 76.2% (95% CI 72.2-79.7), respectively. Patients with pN1 were at the highest risk of 1-year recurrence (1-year DFS 28.6% [95% CI 20.2-40.3]); patients without LNI, but necrosis were at intermediate risk (1-year DFS 62.5% [95% CI 56.9-68.8]); those without LNI and necrosis were at the lowest risk (1-year DFS 83.8% [95% CI 79.1-88.9]). LVI substratification furtherly improved the accuracy in the prediction of early recurrence. CONCLUSIONS: Patients potentially eligible for adjuvant pembrolizumab have worse characteristics and DFS in the off-trial setting as compared to the placebo arm of the KEYNOTE-564. Patients with either LNI or necrosis were at the highest risk of early-recurrence, which make them the ideal candidate to adjuvant pembrolizumab.