Open versus Robot-Assisted Radical Cystectomy for the Treatment of pT4a Bladder Cancer: Comparison of Perioperative Outcomes.

We compared the perioperative outcomes of open (ORC) vs. robot-assisted (RARC) radical cystectomy in the treatment of pT4a MIBC. In total, 212 patients underwent ORC (102 patients, Group A) vs. RARC (110 patients, Group B) for pT4a bladder cancer. Patients were prospectively followed and retrospectively reviewed. We assessed operative time, estimated blood loss (EBL), intraoperative and postoperative complications, length of stay, transfusion rate, and oncological outcomes. Preoperative features were comparable. The mean operative time was 232.8 vs. 189.2 min (p = 0.04), and mean EBL was 832.8 vs. 523.7 mL in Group A vs. B (p = 0.04). An intraoperative transfusion was performed in 32 (31.4%) vs. 11 (10.0%) cases during ORC vs. RARC (p = 0.03). The intraoperative complications rate was comparable. The mean length of stay was shorter after RARC (12.6 vs. 7.2 days, p = 0.02). Postoperative transfusions were performed in 36 (35.3%) vs. 13 (11.8%) cases (p = 0.03), and postoperative complications occurred in 37 (36.3%) vs. 29 (26.4%) patients in Groups A vs. B (p = 0.05). The positive surgical margin (PSM) rate was lower after RARC. No differences were recorded according to the oncological outcomes. ORC and RARC are feasible treatments for the management of pT4a bladder tumors. Minimally invasive surgery provides shorter operative time, bleeding, transfusion rate, postoperative complications, length of stay, and PSM rate.

Partial nephrectomy for renal tumors: recommendations of the Italian Society of Urology RCC working group.

INTRODUCTION: Partial nephrectomy (PN) aims to remove renal tumors while preserving renal function without affecting oncological and perioperative surgical outcomes. Aim of this paper is to summarize the current evidence on PN and to provide evidence-based recommendations on indications, surgical technique, perioperative management and postoperative surveillance of PN for renal tumors in the Italian clinical and health care system context. EVIDENCE ACQUISITION: This review is the result of an interactive peer-reviewing process of the recent literature on PN for renal tumors carried out by an expert panel composed of members of the Italian Society of Urology (SIU) Renal Cell Carcinoma Working Group. EVIDENCE SYNTHESIS: PN for localized renal tumors is not inferior to radical nephrectomy in terms of survival outcomes while significantly better preserving renal function. Loss of renal function after PN is influenced by medical comorbidities/preoperative renal function and surgical variables such volume of parenchyma preserved and ischemia time. Urologists should select the clamping strategy during PN based on their experience and patient-specific factors. PN can be performed with any surgical approach based on surgeon's expertise and skills. Robotic PN has the potential to expand the minimally invasive indications without interfering with oncological outcomes. The use of 3D virtual models, real time ultrasound and fluorescence tools to assess the anatomy and vascularization of renal tumors during PN may allow a more accurate preoperative planning and intraoperative guidance. Proper postoperative surveillance protocols are essential to detect tumor recurrences and assess functional outcomes. CONCLUSIONS: PN is the standard of care for treatment of localized T1 renal tumors. Recent data supports PN also for selected T2-T3a tumors in experienced institutions. Careful preoperative planning, adequate surgical skills and volumes and appropriate postoperative management and surveillance are paramount to optimize PN oncological and functional outcomes.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study.

INTRODUCTION: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. OBJECTIVE: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. METHODS: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann-Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. RESULTS: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1-2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1-3)) and T2 (median LEI 0 (IQR 1-2)). CONCLUSION: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.

Effectiveness of body size stratification for patient exposure optimization in Computed Tomography.

PURPOSE: To establish size-dependent DRL and to estimate the effectiveness of the size-dependent DRLs over size-independent DRLs for a CT exposure optimization process. METHODS: The study included 16,933 adult CT body examinations of the most common CT protocols. Acquisitions were included following an image quality assessment. Patients were grouped into five different classes by means of the water equivalent diameter (Dw): 21 ≤ Dw < 25, 25 ≤ Dw < 29, 29 ≤ Dw < 33,33 ≤ Dw < 37 (in cm). CTDIvol, DLP, DLPtot. and SSDE median values were provided both for the sample as a whole (size-independent approach) and for each Dw class (size-dependent approach). The performance of the two approaches in classifying sub-optimal examinations was evaluated through the confusion matrix and Matthews Correlation Coefficient (MCC) metric. The 75th percentile of the CTDIvol distribution was arbitrarily chosen as a threshold level above which the acquisitions are considered sub-optimal. RESULTS: CTDIvol, DLP, DLPtot and SSDE typical values (median values) are statistically different across Dw groups. The confusion matrix analysis suggests that size-independent DRL could not mark potential suboptimal protocols for small and large patients. The agreement between the size-dependent and size-independent methods is strong only for the most populous classes (MCC > 0.7). For small and large patients size-independent approach fails to identify as sub-optimal around 20 % of the acquisition (MCC≪0.2). CONCLUSIONS: It was proven by means of the confusion matrix and MCC metric that stratifying DRLs by patient size, size-dependent DRL can be a powerful strategy in order to improve the dose optimization process shown that a size-independent DRL fails to identify sub-optimal examinations for small and large patients.

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study.

BACKGROUND: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. METHODS: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann-Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. RESULTS: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804-0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883-0.939; p < 0.01). CONCLUSIONS: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Local Treatment of Recurrent Renal Cell Carcinoma May Have a Significant Survival Effect Across All Risk-of-recurrence Groups.

Background: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. Objective: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. Design setting and participants: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. Intervention: Local treatment of recurrence. Outcome measurements and statistical analysis: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. Results and limitations: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.8), respectively. Limitations include retrospective design. Conclusions: This is the first study assessing the effectiveness of LTR in RCC in a comparable population with RD. This study supports the role of LTR across all RoR groups. Patient summary: We assessed the effectiveness of local treatment of resectable recurrent renal cell carcinoma after surgical treatment of the primary kidney tumour. Local treatment of recurrence was associated with longer survival across groups with a risk of recurrence.

The 2022 Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitor Therapy for Renal Cell Carcinoma.

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. PATIENT SUMMARY: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.

European Association of Urology Guidelines Panel on Renal Cell Carcinoma Update on the New World Health Organization Classification of Kidney Tumours 2022: The Urologist's Point of View.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours published in 2022 will be implemented in the European Association of Urology guidelines on renal cell carcinoma for 2023. Here we provide an update summarising changes in the new WHO classification of renal tumours from a clinician perspective.

A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel.

Over the past decade, only minor changes have been introduced in the TNM staging system for renal cancer. Conversely, many milestones and modifications in management of the disease have been achieved, especially for patients with locally advanced and metastatic cancers. The European Association of Urology guidelines panel proposes a new TNM classification scheme for staging of renal cell carcinoma to reflect these breakthrough clinical improvements.

Management of renal cell carcinoma in transplant kidney: a systematic review and meta-analysis.

INTRODUCTION: After transplantation, approximately 10% of renal cell carcinomas are detected in graft kidneys. These tumors (gRCC) present surgeons with the difficulty of finding a treatment that guarantees both oncological clearance and maintenance of function. We conducted a systematic review and an individual patient data meta-analysis on the oncology, safety and functional outcomes of the available treatments for gRCC. EVIDENCE ACQUISITION: A systematic search was performed across MEDLINE, EMBASE, and Web of Science including any study reporting perioperative, functional and survival outcomes for patients undergoing graft nephrectomy (GN), partial nephrectomy (PN) or thermal ablation (TA) for gRCC. Quade's ANCOVA, Spearman Rho and Pearson χ2, Kaplan-Meier, Log-rank and Standard Cox regression and other tests were used to compare treatments. Studies' quality was evaluated using a modified version of Newcastle Ottawa Scale. EVIDENCE SYNTHESIS: A number of 29 studies (357 patients) were included. No differences between TA and PN were found in terms of safety, functional and oncological outcomes for T1a gRCCs. When applied to pT1b gRCC, PN showed no difference in complications, progression or cancer-specific deaths compared to smaller lesions; PN validity for pT2 gRCCs should be considered unverified due to lack of sufficient evidence. The efficacy and safety of PN or TA for multiple gRCC remain controversial. In case of non-functioning, large (T≥2), complicated or metastatic gRCCs, GN appears to be the most reasonable choice. Quality of evidence ranged from very low to moderate. Studies with large cohorts and longer follow-up are still needed to clarify oncological and functional differences. CONCLUSIONS: PN and TA might be offered as a nephron-sparing treatment in patients with T1a gRCC. There is no significant difference between these options and GN in terms of oncological outcomes and complications. PN and TA offer similar functional outcomes and graft preservation. PN for T1b gRCC seems feasible and safe, but its validity should be considered unverified.

Three-Dimensional Printing Application in a Challenging Case of Type II Endoleak.

PURPOSE: To highlight the importance of 3-dimensional (3D) arterial printing in a case of type II endoleak (EL) embolization. CASE REPORT: An 81-year-old patient, previously treated with endovascular aortic repair (EVAR), developed a type II EL requiring treatment. The EL's main origin was the median sacral artery (MSA). Initial attempts in embolization via a transsealing and transarterial approach were unsuccessful owing to extremely tortuous arterial communications between the left hypogastric artery and the MSA. The construction of a clear resin 3D model of the aorta and iliolumbar arteries improved anatomy understanding and moreover allowed a preoperative simulation. The subsequent transarterial attempt in embolization was resolutive, significantly reducing total procedural time and radiation dose. CONCLUSION: Printing of clear resin 3D arterial models facilitates type II EL transarterial embolization, improving anatomy understanding and allowing simple fluoroscopy-free simulations. CLINICAL IMPACT: The aim of our work is to highlight the additional value of three-dimensional (3D) printing during preoperative planning of challenging endovascular cases. To our best knowledge, this is the first report about 3D printing use in a case of type II endoleak (EL). We believe that realizing life-size aortic models in selected cases where a complex type II EL embolization procedure is indicated, could lead to a better understanding of arterial anatomy, thus allowing to increase procedural success and reduce operative and most importantly fluoroscopy time.

Recurrence pattern in localized RCC: results from a European multicenter database (RECUR).

INTRODUCTION: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern. MATERIAL AND METHODS: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed. RESULTS: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18-3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01-1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64-1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study. CONCLUSIONS: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.

Non-timely clinically applicable ADC ratio in prostate mpMRI: a comparison with fusion biopsy results.

PURPOSE: The purpose of the study was to assess the diagnostic accuracy of ADC ratio and to evaluate its efficacy in reducing the number of false positives in prostatic mpMRI. MATERIALS AND METHODS: All patients who underwent an mpMRI and a targeted fusion biopsy in our institution from 2016 to 2021 were retrospectively selected. Two experienced readers (R1 and R2) independently evaluated the images, blindly to biopsy results. The radiologists assessed the ADC ratios by tracing a circular 10 mm2 ROI on the biopsied lesion and on the apparently benign contralateral parenchyma. Prostate cancers were divided into non-clinically significant (nsPC, Gleason score = 6) and clinically significant (sPC, Gleason score ≥ 7). ROC analyses were performed. RESULTS: 167 patients and188 lesions were included. Concordance was 0.62 according to Cohen's K. ADC ratio showed an AUC for PCAs of 0.78 in R1 and 0.8 in R2. The AUC for sPC was 0.85 in R1 and 0.84 in R2. The 100% sensitivity cut-off for sPCs was 0.65 (specificity 25.6%) in R1 and 0.66 (specificity 27.4%) in R2. Forty-three benign or not clinically significant lesions were above the 0.65 threshold in R1; 46 were above the 0.66 cut-off in R2. This would have allowed to avoid an equal number of unnecessary biopsies at the cost of 2 nsPCs in R1 and one nsPC in R2. CONCLUSION: In our sample, the ADC ratio was a useful and accurate tool that could potentially reduce the number of false positives in mpMRI.

Apremilast retention rate in clinical practice: observations from an Italian multi-center study.

OBJECTIVE: There are few real-world setting studies focused on apremilast effectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention rate in real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and the factors related to treatment persistence. METHODS: In fifteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value < 0.05 was considered statistically significant. RESULTS: The 356 enrolled patients (median age 60 [interquartile range IQR 52-67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7-34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefficacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefficacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96-0.99; p = 0.048 and 0.54 IQR 0.31-0.95; p = 0.03). CONCLUSION: Almost three-fifths of PsA patients receiving apremilast were still in treatment after 3 years. This study confirmed its effectiveness and safety profile. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbidities. Key Points • Apremilast retention rates in this real-life cohort and trials are comparable. • The oligo-articular phenotype is associated with long-lasting treatment (i.e., 3 years). • No different or more prevalent adverse events were observed.

Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3-G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Predictors of Positive Surgical Margins after Robot-Assisted Partial Nephrectomy for Localized Renal Tumors: Insights from a Large Multicenter International Prospective Observational Project (The Surface-Intermediate-Base Margin Score Consortium).

Background: To explore predictors of positive surgical margins (PSM) after robotic partial nephrectomy (PN) in a large multicenter international observational project, harnessing the Surface-Intermediate-Base (SIB) margin score to report the resection technique after PN in a standardized way. Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with PN from September 2014 to March 2015 at 16 tertiary referral centers and included in the SIB margin score International Consortium were prospectively collected. For the present study, only patients treated with robotic PN were included. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of PSMs after PN. Results: Overall, 289 patients were enrolled. Median (IQR) preoperative tumor size was 3.0 (2.3−4.2) cm and median (IQR) PADUA score was 8 (7−9). SIB scores of 0−2 (enucleation), 3−4 (enucleoresection) and 5 (resection) were reported in 53.3%, 27.3% and 19.4% of cases, respectively. A PSM was recorded in 18 (6.2%) patients. PSM rate was 4.5%, 11.4% and 3.6% in case of enucleation, enucleoresection and resection, respectively. Patients with PSMs had tumors with a higher rate of contact with the urinary collecting system (55.6% vs. 27.3%; p < 0.001) and a longer median warm ischemia time (22 vs. 16 min; p = 0.02) compared with patients with negative surgical margins, while no differences emerged between the two groups in terms of other tumor features (i.e., pathological diameter, PADUA score). In multivariable analysis, only enucleoresection (SIB score 3−4) versus enucleation (SIB score 0−2) was found to be an independent predictor of PSM at final pathology (HR: 2.68; 95% CI: 1.25−7.63; p = 0.04), while resection (SIB score 5) was not. Conclusions: In our experience, enucleoresection led to a higher risk of PSMs as compared to enucleation. Further studies are needed to assess the differential impacts of resection technique and surgeon's experience on margin status after robotic PN.

Impact of Trifecta definition on rates and predictors of "successful" robotic partial nephrectomy for localized renal masses: results from the Surface-Intermediate-Base Margin Score International Consortium.

BACKGROUND: Over the years, five different Trifecta score definitions have been proposed to optimize the framing of "success" in partial nephrectomy (PN) field. However, such classifications rely on different metrics. The aim of the present study was to explore how the success rate of robotic PN, as well as its drivers, vary according to the currently available definitions of Trifecta. METHODS: Data from consecutive patients with cT1-2N0M0 renal masses treated with robotic PN at 16 referral centers from September 2014 to March 2015 were prospectively collected. Trifecta rate was defined for each of the currently available definitions. Multivariable logistic regression analysis was used to evaluate possible predictors of "Trifecta failure" according to the different adopted formulation. RESULTS: Overall, 289 patients met the inclusion criteria. Among the definitions, Trifecta rates ranged between 66.4% and 85.9%. Multivariable analysis showed that predictors for "Trifecta failure" were mainly tumor-related (i.e. tumor's nephrometry) for those Trifecta scores relying on WIT as a surrogate metric for postoperative renal function deterioration (definitions 1,2), while mainly surgery-related (i.e. ischemia time and excision strategy) for those including the percentage change in postoperative eGFR as the functional cornerstone of Trifecta (definitions 3-5). CONCLUSIONS: There was large variability in rates and predictors of "unsuccessful PN" when using different Trifecta scores. Further research is needed to improve the value of the Trifecta metrics, integrating them into routine patient counseling and standardized assessment of surgical quality across institutions.