3D virtual model for robot-assisted partial nephrectomy in highly-complex cases (PADUA ⩾ 10).

PURPOSE: To compare two cohorts of patients submitted to robot-assisted partial nephrectomy (RAPN) for highly-complex renal masses (PADUA ⩾ 10) with versus without the use of 3DVMs. MATERIALS AND METHODS: We screened a prospective consecutive cohort of 152 patients submitted to RAPN with 3DVM and 1264 patients submitted to RAPN without 3DVM between 2019 and 2022. Only PADUA ⩾ 10 cases were considered eligible for analysis. Propensity score matching (PSM) analysis was applied. Primary endpoint was to evaluate whereas RAPNs with 3DVM were superior in terms of functional outcomes at 12-month. Secondary outcomes were to compare perioperative and oncological outcomes. Multivariable logistic regression analyses (MVA) tested the associations of clinically significant eGFR drop and 3DVMs. Subgroups analysis was performed for PAUDA-risk categories. RESULTS: Thirty seven patients for each group were analyzed after PSM. RAPN with 3DVM presented a higher rate of selective/no clamping procedure (32.5% vs 16.2%, p = 0.03) and a higher enucleation rate (43.2% vs 29.8%, p = 0.04). Twelve-month functional preservation performed better within 3DVM group in terms of creatinine serum level (median 1.2 [IQR 1.1-1.4] vs 1.6 [IQR 1.1-1.8], p = 0.03) and eGFR (median 64.6 [IQR 56.2-74.1] vs 52.3 [IQR 49.2-74.1], p = 0.03). MVA confirmed 3DVM as a protective factor for clinically significant eGFR drop in this subgroup of patients. CONCLUSIONS: RAPN performed with the use of 3DVM assistance for PADUA ⩾ 10 cases resulted in lower incidence of global ischemia and higher rate of enucleations. The positive impact of such technology was found at 12-month follow-up.

Three-dimensional virtual model for robot-assisted partial nephrectomy: a propensity-score matching analysis with a contemporary control group.

PURPOSE: To compare two cohorts of patients submitted to robot-assisted partial nephrectomy (RAPN) with vs without the use of three-dimensional virtual models (3DVMs). METHODS: We screened a prospective consecutive cohort of 152 patients submitted to RAPN with 3DVM and 1264 patients submitted to RAPN without 3DVM between 2019 and 2022. Propensity score matching analysis (PSMA) was applied. Primary endpoint was to evaluate whereas RAPNs with 3DVM were superior in terms of functional outcomes at 12-month. Secondary endopoints were to compare perioperative and oncological outcomes. Multivariable logistic regression analyses (MVA) tested the associations of clinically significant eGFR drop and 3DVMs. Subgroups analysis was performed for PAUDA-risk categories. RESULTS: 100 patients for each group were analyzed after PSMA. RAPN with 3DVM presented a higher rate of selective/no clamping procedure (32% vs 16%, p = 0.03) and a higher enucleation rate (40% vs 29%, p = 0.04). As concern to primary endopoint, 12-month functional preservation performed better within 3DVM group in terms of creatinine serum level (median 1.2 [IQR 1.1-1.4] vs 1.6 [IQR 1.1-1.8], p = 0.03) and eGFR (median 64.6 [IQR 56.2-74.1] vs 52.3 [IQR 49.2-74.1], p = 0.03). However, this result was confirmed only in the PADUA ≥ 10 renal masses. Regarding secondary endpoints, no significative difference emerged between the two cohorts. MVA confirmed 3DVM as a protective factor for clinically significant eGFR drop only in high-risk (PADUA ≥ 10) masses. CONCLUSIONS: RAPN performed with the use of 3DVM assistance resulted in lower incidence of global ischemia and higher rate of enucleations. The positive impact of such technology was found at 12-month only in high-risk renal masses.

Step by step technique of Stentless Florence Robotic Intracorporeal Neobladder (FloRIN), does the ureteral management influence functional outcomes?

INTRODUCTION: Benefits and harms of avoid the sent placement during IntraCorporeal Neobladder configuration are still debated. Our objective was to describe the step-by-step technique of Florence intracorporeal neobladder (FloRIN) configuration performed with stentless procedure focusing on perioperative and mid-term functional outcomes. MATERIALS AND METHODS: In this single institution prospective randomized 1:1 series all consecutive patients underwent Robot-Assisted Radical Cystectomy (RARC) and FloRIN reconfiguration from January 2021 to March 2021 were enrolled. Functional perioperative and mid-term outcomes were gathered. Postoperative complications were graded according to Clavien-Dindo classification and divided in early (<30 days from discharge) and delayed (>30 days). RESULTS: Overall, 10 patients were included in the analysis. Of these, the 50.0% was treated with Stentless FloRIN. In terms of baseline features, no differences were recorded between the two groups. Median age was 65 and 66 years while median BMI was 27 and 25 in the stentless and in the stent group, respectively. Concerning intraoperative variables, no intraoperative complications as well as open conversion occurred among both groups. As regard introperative features, a shorter console time was associated with stentless procedure (331 min vs 365 min). In terms of perioperative outcomes, canalization and time to drainage removal didn't differ between groups while length of hospital stay was significantly lower in stentless group 10 days versus 14 days. Early and delayed postoperative complication rate was not influenced by the ureteral management at a preliminary assessment with comparable rates of Clavien Dindo ⩾ 3a between the two groups. Mid-term functional outcomes did not differ between groups in terms of kidney function loss. CONCLUSIONS: FloRIN with Stentless technique showed functional and perioperative preliminary outcomes comparable with the standard ureteral management strategy. Further series with longer functional follow-up assessment will be needed to confirm our preliminary results.

Minimally invasive transperitoneal partial versus radical nephrectomy in obese patients: perioperative and long-term functional outcomes from a large perspective contemporary series (RECORd2 project).

BACKGROUND: The aim of this study is to evaluate the perioperative and long-term functional outcomes of laparoscopic (LPN) and robot-assisted partial nephrectomy (RAPN) in comparison to laparoscopic radical nephrectomy (LRN) in obese patients diagnosed with renal cell carcinoma. METHODS: Clinical data of 4325 consecutive patients from The Italian REgistry of COnservative and Radical Surgery for cortical renal tumor Disease (RECORD 2 Project) were gathered. Only patients treated with transperitoneal LPN, RAPN, or LRN with Body Mass Index (BMI) ≥30 kg/m2, clinical T1 renal tumor and preoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min, were included. Perioperative, and long-term functional outcomes were examined. RESULTS: Overall, 388 patients were included, of these 123 (31.7%), 120 (30.9%) and 145 (37.4%) patients were treated with LRN, LPN, and RAPN, respectively. No significant difference was observed in preoperative characteristics. Overall, intra and postoperative complication rates were comparable among the groups. The LRN group had a significantly increased occurrence of acute kidney injury (AKI) compared to LPN and RAPN (40.6% vs. 15.3% vs. 7.6%, P=0.001). Laparoscopic RN showed a statistically significant higher renal function decline at 60-month follow-up assessment compared to LPN and RAPN. A significant renal function loss was recorded in 30.1% of patients treated with LRN compared to 16.7% and 10.3% of patients treated with LPN and RAPN (P=0.01). CONCLUSIONS: In obese patients, both LPN and RAPN showcased comparable complication rates and higher renal function preservation than LRN. These findings highlighted the potential benefits of minimally invasive PN over radical surgery in the context of obese individuals.

Is it safe to defer prostate cancer treatment? Assessing the impact of surgical delay on the risk of pathological upstaging after robot-assisted radical prostatectomy.

INTRODUCTION: We sought to investigate whether surgical delay may be associated with pathological upstaging in patients treated with robot assisted radical prostatectomy (RARP) for localized and locally advanced prostate cancer (PCa). MATERIALS AND METHODS: Consecutive firstly-diagnosed PCa patients starting from March 2020 have been enrolled. All the patients were categorized according to EAU risk categories for PCa risk. Uni- and multivariate analysis were fitted to explore clinical and surgical predictors of pathological upstaging to locally advanced disease (pT3/pT4 - pN1 disease). RESULTS: Overall 2017 patients entered the study. Median age at surgery was 68 (IQR 63-73) years. Overall low risk, intermediate risk, localized high risk and locally advanced disease were recorded in 368 (18.2 %), 1071 (53.1 %), 388 (19.2 %) and 190 (9.4 %), respectively. Median time from to diagnosis to treatment was 51 (IQR 29-70) days. Time to surgery was 56 (IQR 32-75), 52 (IQR 30-70), 45 (IQR 24-60) and 41 (IQR 22-57) days for localized low, intermediate and high risk and locally advanced disease, respectively. Considering 1827 patients with localized PCa, at multivariate analysis ISUP grade group ≥4 on prostate biopsy (HR: 1.30; 95 % CI 1.07-1.86; p = 0.02) and surgical delay only in localized high-risk disease (HR: 1.02; 95 % CI 1.01-1.54; p = 0.02) were confirmed as independent predictors of pathological upstaging to pT3-T4/pN1 disease at final histopathological examination. CONCLUSIONS: In localized high-risk disease surgical delay could be associated with a higher risk of adverse pathologic findings.

A systematic review and meta-analysis to evaluate the diagnostic accuracy of PSMA PET/CT in the initial staging of prostate cancer.

BACKGROUND: Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging. METHODS: Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI. RESULTS: A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies. CONCLUSIONS: The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project.

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

Does the Timing of Cytoreductive Nephrectomy Impact Outcomes? Analysis of REMARCC Registry Data for Patients Receiving Tyrosine Kinase Inhibitor Versus Immune Checkpoint Inhibitor Therapy.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy. Conclusions and clinical implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC. Patient summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.

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.

The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

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.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Time to progression is the main predictor of survival in patients with high-risk nonmuscle invasive bladder cancer: Results from a machine learning-based analysis of a large multi-institutional database.

BACKGROUND: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints. METHODS: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality. RESULTS: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference). CONCLUSION: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design.

Off-clamp Versus On-clamp Partial Nephrectomy: Re-envision of a Dilemma.

We contextualize controversial evidence on the impact of warm ischemia on functional outcomes after partial nephrectomy for localized renal tumors and provide a holistic framework for re-envisioning the dilemma of off-clamp versus on-clamp surgery. The focus should shift away from the surgeon towards patient- and kidney-related characteristics.

Development and internal validation of a nomogram predicting 3-year chronic kidney disease upstaging following robot-assisted partial nephrectomy.

PURPOSE: Aim of the present study was to develop and validate a nomogram to accurately predict the risk of chronic kidney disease (CKD) upstaging at 3 years in patients undergoing robot-assisted partial nephrectomy (RAPN). METHODS: A multi-institutional database was queried to identify patients treated with RAPN for localized renal tumor (cT1-cT2, cN0, cM0). Significant CKD upstaging (sCKD-upstaging) was defined as development of newly onset CKD stage 3a, 3b, and 4/5. Model accuracy was calculated according to Harrell C-index. Subsequently, internal validation using bootstrapping and calibration was performed. Then nomogram was depicted to graphically calculate the 3-year sCKD-upstaging risk. Finally, regression tree analysis identified potential cut-offs in nomogram-derived probability. Based on this cut-off, four risk classes were derived with Kaplan-Meier analysis tested this classification. RESULTS: Overall, 965 patients were identified. At Kaplan-Meier analysis, 3-year sCKD-upstaging rate was 21.4%. The model included baseline (estimated glomerular filtration rate) eGFR, solitary kidney status, multiple lesions, R.E.N.A.L. nephrometry score, clamping technique, and postoperative acute kidney injury (AKI). The model accurately predicted 3-year sCKD-upstaging (C-index 84%). Based on identified nomogram cut-offs (7 vs 16 vs 26%), a statistically significant increase in sCKD-upstaging rates between low vs intermediate favorable vs intermediate unfavorable vs high-risk patients (1.3 vs 9.2 vs 22 vs 54.2%, respectively, p < 0.001) was observed. CONCLUSION: Herein we introduce a novel nomogram that can accurately predict the risk of sCKD-upstaging at 3 years. Based on this nomogram, it is possible to identify four risk categories. If externally validated, this nomogram may represent a useful tool to improve patient counseling and management.