Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome.

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5-8% of all kidney cancer cases and is associated with syndromes such as von Hippel-Lindau syndrome, Birt-Hogg-Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available.

Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence.

Kidney stone disease (KSD) is one of the most common urological diseases. The incidence of kidney stones has increased dramatically in the last few decades. Kidney stones are mineral deposits in the calyces or the pelvis, free or attached to the renal papillae. They contain crystals and organic components, and they are made when urine is supersaturated with minerals. Calcium-containing stones are the most common, with calcium oxalate as the main component of most stones. However, many of these form on a calcium phosphate matrix called Randall's plaque, which is found on the surface of the kidney papilla. The etiology is multifactorial, and the recurrence rate is as high as 50% within 5 years after the first stone onset. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. This review aims to understand the pathophysiology and the main molecular mechanisms known to date to prevent recurrences, which requires behavioral and nutritional interventions, as well as pharmacological treatments that are specific to the type of stone.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

Efficacy and safety profile of GreenLight laser photoselective vaporization of the prostate in ≥ 75 years old patients: results from the Italian GreenLight Laser Study Group.

BACKGROUND: Benign Prostatic Obstruction (BPO) is the most common non-malignant urological condition among men and its incidence rise with age. Among prostate treatments, GreenLight laser seems to reduce bleeding and would be safer in the aging population. AIMS: We aimed to compare the functional outcomes and safety profile of < 75 years old (Group A) and ≥ 75 years old (Group B) patients. METHODS: In a multicenter setting, we retrospectively analyzed all the patients treated with GreenLight Laser vaporization of the prostate (PVP). RESULTS: 1077 patients were eligible for this study. 757 belonged to Group A (median age 66 years) and 320 to Group B (median age 78 years). No differences were present between the two groups in terms of prostate volume, operative time, hospital stay, PSA decrease over time after surgery, complications and re-intervention rate with a median follow-up period of 18 months (IQR 12-26). Nevertheless, focusing on complications, GreenLight laser PVP demonstrated an excellent safety profile in terms of hospital stay, re-intervention and complications, with an overall 29.6% complication rate in older patients and only two cases of Clavien III. Functional outcomes were similar at 12 month and became in favor of Group A over time. These data are satisfactory with a Qmax improvement of 111.7% and an IPSS reduction of 69.5% in older patients. DISCUSSION AND CONCLUSIONS: GreenLight laser photoselective vaporization of the prostate is a safe and efficient procedure for all patients, despite their age, with comparable outcomes and an equal safety profile.

Radiogenomics in Renal Cancer Management-Current Evidence and Future Prospects.

Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice.

Multiparametric Ultrasound Diagnostic Approach to Malignancy-Mimicking Adenomatoid Tumors of the Scrotum: Is Strain Elastography Enough?

Background: Paratesticular tumors (PTs) are very uncommon, accounting for almost 5% of intrascrotal tumors. Of these, adenomatoid tumors (ATs) represent about 30% and most frequently arise in the tail of the epididymis. Ultrasound (US) examination is the first-choice imaging method employed for the evaluation of the scrotum. Unfortunately, there are no specific US-imaging features useful for distinguishing an AT from a malignant lesion. To increase diagnostic accuracy and confidence, new sonographic techniques have incorporated real-time tissue elastography (RTE) under the assumption that malignant lesions are "harder" than benign lesions. Case report: In our paper, we describe a very rare case of a 60-year-old patient with a giant paratesticular mass mimicking malignancy when examined using RTE, i.e., it was stiffer than the surrounding tissue (a hard pattern), which, upon histologic examination, was identified as an AT. Discussion: Our case underscores that there is also a significant overlap between different types of scrotal lesions when RTE is used for examination. Thus, if a PT is found, the imaging approach should always be supplemented with more definitive diagnostic methods, such as FNAC or FNAB, which are the only diagnostic methods capable of leading to a certain diagnosis. Conclusions: Alongside underlining the importance of pre-operative imaging for making correct diagnoses and selecting the correct therapy, we wish to draw our readers' attention to this report in order to demonstrate the clinical implications of a giant AT presenting as stiff lesions when examined using SE.

Is off-clamp robot-assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial.

OBJECTIVES: To compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT). MATERIALS AND METHODS: The CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT02287987) is a multicentre RCT including patients with normal baseline function, two kidneys and masses with RENAL scores ≤ 10. Pre- and postoperative renal scintigraphy was prescribed. Renal defatting and hilum isolation were required in both study arms; in the on-clamp arm, ischaemia was imposed until the completion of medullary renorraphy, while in the off-clamp condition it was not allowed throughout the procedure. The primary endpoint was 6-month absolute variation in estimated glomerular filtration rate (AV-GFR); secondary endpoints were: 12, 18 and 24-month AV-GFR; 6-month estimated glomerular filtration rate variation >25% rate (RV-GFR >25); and absolute variation in ipsilateral split renal function (AV-SRF). The planned sample size was 102 + 102 cases, after taking account crossover of cases to the alternate study arm; a 1:1 randomization was performed. AV-GFR and AV-SRF were compared using analysis of covariation, and RV-GFR >25 was assessed using multivariable logistic regression. Intention-to-treat (ITT) and per-protocol analyses (PP) were performed. RESULTS: A total of 160 and 164 patients were randomly assigned to on- and off-clamp RAPN, respectively; crossover was observed in 14% and 43% of the on- and off-clamp arms, respectively. We were unable to find any statistically significant difference between on- vs off-clamp with regard to the primary endpoint (ITT: 6-month AV-GFR -6.2 vs -5.1 mL/min, mean difference 0.2 mL/min, 95% confidence interval [CI] -3.1 to 3.4 [P = 0.8]; PP: 6-month AV-GFR -6.8 vs -4.2 mL/min, mean difference 1.6 mL/min, 95% CI -2.3 to 5.5 [P = 0.7]) or with regard to the secondary endpoints. The median warm ischaemia time was 14 vs 15 min in the ITT analysis and 14 vs 0 min in the PP analysis. CONCLUSION: In patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on- vs off-clamp RAPN.

Simultaneous robotic partial nephrectomy for bilateral renal masses.

PURPOSE: There is currently no consensus regarding the optimal treatment strategy for patients presenting with synchronous bilateral renal masses. The decision to perform bilateral procedures on the same intervention or in staged procedures is debated. The aim of this manuscript is to analyse the outcomes of simultaneous robot-assisted partial nephrectomy (RAPN) in a series of patients with bilateral renal masses treated at five Italian robotic institutions. METHODS: Data from a prospectively maintained multi-institutional database on patients subjected to simultaneous RAPN between November 2011 and July 2019 were reviewed. RAPNs were performed with da Vinci Si or Xi surgical system by expert robotic surgeons. Baseline demographics and clinical features, peri- and post-operative data were collected. RESULTS: Overall, 27 patients underwent simultaneous bilateral RAPN, and 54 RAPNs were performed without need of conversion; median operative time was 250 minutes, median estimated blood loss was 200 mL. Renal artery clamping was needed for 27 (50%) RAPNs with a median warm ischemia time of 15 minutes and no case of acute kidney injury. Complications were reported in 7 (25.9%) patients, mainly represented by Clavien 2 events (6 blood transfusions). Positive surgical margins were assessed in 2 (3.7%) of the renal cell carcinoma. At the median follow-up of 30 months, recurrence-free survival was 100%. CONCLUSION: Our data showed that, in selected patients and expert hands, simultaneous bilateral RAPNs could be a safe and feasible procedure with promising results for the treatment of bilateral synchronous renal masses.

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium).

PURPOSE: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. RESULTS: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up. CONCLUSION: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

Prediction of significant renal function decline after open, laparoscopic, and robotic partial nephrectomy: External validation of the Martini's nomogram on the RECORD2 project cohort.

OBJECTIVES: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini's nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. METHODS: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini's nomogram were applied to each approach predicting renal function loss at all the specific timeframes. RESULTS: Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was <70% at 48 months of follow-up. CONCLUSIONS: Martini's nomogram is a valid tool for predicting the decline in renal function at 6 and 12 months after robot-assisted partial nephrectomy and laparoscopic partial nephrectomy, whereas it showed a lower performance at longer follow-up and in patients treated with open approach at all these time cutoffs.

Bladder cancer: do we need contrast injection for MRI assessment of muscle invasion? A prospective multi-reader VI-RADS approach.

OBJECTIVES: (1) To investigate whether a contrast-free biparametric MRI (bp-MRI) including T2-weighted images (T2W) and diffusion-weighted images (DWI) can be considered an accurate alternative to the standard multiparametric MRI (mp-MRI), consisting of T2, DWI, and dynamic contrast-enhanced (DCE) imaging for the muscle-invasiveness assessment of bladder cancer (BC), and (2) to evaluate how the diagnostic performance of differently experienced readers is affected according to the type of MRI protocol. METHODS: Thirty-eight patients who underwent a clinically indicated bladder mp-MRI on a 3-T scanner were prospectively enrolled. Trans-urethral resection of bladder was the gold standard. Two sets of images, set 1 (bp-MRI) and set 2 (mp-MRI), were independently reviewed by four readers. Descriptive statistics, including sensitivity and specificity, were calculated for each reader. Receiver operating characteristic (ROC) analysis was performed, and the areas under the curve (AUCs) were calculated for the bp-MRI and the standard mp-MRI. Pairwise comparison of the ROC curves was performed. RESULTS: The AUCs for bp- and mp-MRI were respectively 0.91-0.92 (reader 1), 0.90 (reader 2), 0.95-0.90 (reader 3), and 0.90-0.87 (reader 4). Sensitivity was 100% for both protocols and specificity ranged between 79.31 and 89.66% and between 79.31 and 83.33% for bp-MRI and mp-MRI, respectively. No significant differences were shown between the two MRI protocols (p > 0.05). No significant differences were shown accordingly to the reader's experience (p > 0.05). CONCLUSIONS: A bp-MRI protocol consisting of T2W and DWI has comparable diagnostic accuracy to the standard mp-MRI protocol for the detection of muscle-invasive bladder cancer. The experience of the reader does not significantly affect the diagnostic performance using VI-RADS. KEY POINTS: • The contrast-free MRI protocol shows a comparable accuracy to the standard multiparametric MRI protocol in the bladder cancer muscle-invasiveness assessment. • VI-RADS classification helps non-expert radiologists to assess the muscle-invasiveness of bladder cancer. • DCE should be carefully interpreted by less experienced readers due to inflammatory changes representing a potential pitfall.

Biomarkers for Renal Cell Carcinoma Recurrence: State of the Art.

PURPOSE OF REVIEW: We aim to summarize the current state of art about the possible use of biomarkers for predicting renal cell carcinoma (RCC) recurrence after curative treatment. In addition, we aim to provide a snapshot about the clinical implication of biomarkers use for follow-up planification. RECENT FINDINGS: A wide variety of biomarkers have been proposed. RCC biomarkers have been individuated in tumoral tissue, blood, and urine. A variety of molecules, including proteins, DNA, and RNA, warrant a good accuracy for RCC recurrence and progression prediction. Their use in prediction models might warrant a better patients' risk stratification. Future prognostic models will probably include a combination of classical features (tumor grade, stage, etc.) and novel biomarkers. Such models might allow a more accurate treatment and follow-up planification.

New Antiandrogen Compounds Compared to Docetaxel for Metastatic Hormone Sensitive Prostate Cancer: Results from a Network Meta-Analysis.

PURPOSE: Docetaxel represent the standard of care in patients with metastatic, hormone sensitive prostate cancer. However, androgen receptor axis targeted therapies have also been shown to be effective. We aimed to analyze findings in randomized controlled trials investigating first-line treatment for hormone sensitive prostate cancer. MATERIALS AND METHODS: We systematically reviewed the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and the PICO (Population, Intervention, Comparator, Outcomes) methodology. Outcomes of interest were overall and progression-free survival, and the rate of high grade adverse events. RESULTS: No treatment was superior to docetaxel in terms of overall survival. However, abiraterone (HR 0.89, 95% CI 0.76-1.05), enzalutamide (HR 0.90, 95% CI 0.69-1.19) and apalutamide (HR 0.90, 95% CI 0.67-1.22) showed nonstatistically significant lower overall mortality rates than docetaxel. Abiraterone (HR 0.71, 95% CI 0.59-0.86), enzalutamide (HR 0.61, 95% CI 0.49-0.75) and apalutamide (HR 0.74, 95% CI 0.57-0.95) also showed statistically significant lower disease progression rates than docetaxel. Furthermore, abiraterone (OR 0.83, 95% CI 0.56-1.21) showed no statistically significant lower rate of high grade adverse events compared to docetaxel. Finally, enzalutamide (OR 0.56, 95% CI 0.35-0.92) and apalutamide (OR 0.44, 95% CI 0.24-0.79) showed statistically significant lower rates of high grade adverse events compared to docetaxel. CONCLUSIONS: Treatment with androgen receptor axis targeted therapies combined with androgen deprivation therapy in patients with hormone sensitive prostate cancer did not offer a statistically significant advantage in overall survival compared to the standard, docetaxel. However, it was associated with a lower disease progression rate. Moreover, apalutamide and enzalutamide offer a better safety profile.

Robotic partial nephrectomy vs minimally invasive radical nephrectomy for clinical T2a renal mass: a propensity score-matched comparison from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

OBJECTIVE: To compare outcomes of minimally invasive radical nephrectomy (MIS-RN) and robot-assisted partial nephrectomy (RAPN) in clinical T2a renal mass (cT2aRM). PATIENTS AND METHODS: Retrospective, multicentre, propensity score-matched (PSM) comparison of RAPN and MIS-RN for cT2aRM (T2aN0M0). Cohorts were PSM for age, sex, body mass index, American Society of Anesthesiologists (ASA) class, clinical tumour size, and R.E.N.A.L. score using a 2:1 ratio for RN:PN. The primary outcome was disease-free survival (DFS). Secondary outcomes included overall survival (OS), complication rates, and de novo estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 . Multivariable (MVA) and Kaplan-Meier survival analyses (KMSA) were conducted. RESULTS: In all, 648 patients (216 RAPN/432 MIS-RN) were matched. There were no significant differences in intraoperative complications (P = 0.478), Clavien-Dindo Grade ≥III complications (P = 0.063), and re-admissions (P = 0.238). The MVA revealed high ASA class (hazard ratio [HR] 2.7, P = 0.044) and sarcomatoid (HR 5.3, P = 0.001), but not surgery type (P = 0.601) to be associated with all-cause mortality. Increasing R.E.N.A.L. score (HR 1.31, P = 0.037), high tumour grade (HR 2.5, P = 0.043), and sarcomatoid (HR 2.8, P = 0.02) were associated with recurrence, but not surgery (P = 0.555). Increasing age (HR 1.1, P < 0.001) and RN (HR 3.9, P < 0.001) were predictors of de novo eGFR of <45 mL/min/1.73 m2 . Comparing RAPN and MIS-RN, KMSA revealed no significant differences for 5-year OS (76.3% vs 88.0%, P = 0.221) and 5-year DFS (78.6% vs 85.3%, P = 0.630) for pT2 RCC, and no differences for 3-year OS (P = 0.351) and 3-year DFS (P = 0.117) for pT3a upstaged RCC. The 5-year freedom from de novo eGFR of <45 mL/min/1.73 m2 was 91.6% for RAPN vs 68.9% for MIS-RN (P < 0.001). CONCLUSIONS: RAPN had similar oncological outcomes and morbidity profile as MIS-RN, while conferring functional benefit. RAPN may be considered as a first-line option for cT2aRM.

Safety of on- vs off-clamp robotic partial nephrectomy: per-protocol analysis from the data of the CLOCK randomized trial.

PURPOSE: To compare the safety of on- vs off-clamp robotic partial nephrectomy (RAPN). METHODS: 302 patients with RENAL masses ≤ 10 were randomized to undergo on-clamp (150) vs off-clamp (152) RAPN (CLOCK trial-ClinicalTrials.gov NCT02287987) at seven institutions by one experienced surgeon per institution. Intra-operative data, complications, and positive surgical margins were compared. RESULTS: Due to a relevant rate of shift from the assigned treatment, the per-protocol analysis only was considered and the data from 129 on-clamp vs 91 off-clamp RAPNs analyzed. Tumor size (off-clamp vs on-clamp, 2.2 vs 3.0 cm, p < 0.001) and RENAL score (5 vs 6, p < 0.001) significantly differed. At univariate analysis, no differences were found regarding intra-operative estimated blood loss (off- vs on-clamp, 100 vs 100 ml, p = 0.7), post-operative complications rate (19% vs 26%, p = 0.2), post-operative anemia (Hb decrease > 2.5 g/dl 26% vs 27%, p = 0.9; transfusion rate 3.4% vs 6.3%, p = 0.5; re-intervention due to bleeding 1.1% vs 4%, p = 0.4), acute kidney injury (4% vs 6%, p = 0.8), and positive surgical margins (3.5% vs 8.2%, p = 0.1). At multivariate analysis accounting for tumor diameter and complexity, considering the on-clamp group as the reference category, a significant difference was noted in the off-clamp group exclusively for blood loss (OR 0.3, 95% CI 0.09-0.52, p = 0.008). CONCLUSIONS: The on-clamp and off-clamp approaches for RAPN showed a comparable safety profile.

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort.

PURPOSE: To provide a snapshot of toxicities and oncologic outcomes of Abiraterone (AA) and Enzalutamide (EZ) in a chemo-naïve metastatic castration-resistant prostate cancer (mCPRC) population from a longitudinal real-life multicenter cohort. METHODS: We prospectively collected data on chemo-naïve mCRPC patients treated with AA or EZ. Primary outcomes were PSA response, oncologic outcomes and toxicity profile. The Kaplan-Meier method was used to compare differences in terms of progression-free survival (PFS) between AA vs EZ and high- vs low-volume disease cohorts. Univariable and multivariable Cox regression analyses were performed to identify predictors of PFS. Toxicity, PSA response rates and oncologic outcomes on second line were compared with those observed on first line. RESULTS: Out of 137 patients, 88 received AA, and 49 EZ. On first line, patients receiving EZ had significantly higher PSA response compared with AA (95.9% vs 67%, p < 0.001), comparable toxicity rate (10.2% vs 16.3%, p = 0.437) and PFS probabilities (p = 0.145). Baseline PSA and high-volume disease were predictors of lower PFS probabilities at univariable analysis (p = 0.027 and p = 0.007, respectively). Overall, 28 patients shifted to a second-line therapy (EZ or radiometabolic therapy). Toxicity and PSA response rates on second line were comparable to those observed on first line (11.1% vs 12.4%, p = 0.77; 73.1% vs 77.4%, p = 0.62, respectively); 2-year PFS, cancer-specific and overall survival probabilities were comparable to those displayed in first-line cohort (12.1% vs 16.2%, p = 0.07; 85.7% vs 86.4%, p = 0.98; 71% vs 80.3%, p = 0.66, respectively). CONCLUSIONS: Toxicity profile, PSA response rate and oncological outcomes were comparable between first-line and second-line courses in patients treated with either AA or EZ for mCRPC. Our findings showed the tolerability and oncological effectiveness, when feasible, of two lines of therapy other than chemotherapy.

External validation of Cormio nomogram for predicting all prostate cancers and clinically significant prostate cancers.

PURPOSE: Recently, the Cormio et al. nomogram has been developed to predict prostate cancer (PCa) and clinically significant PCa using benign prostatic obstruction parameters. The aim of the present study was to externally validate the nomogram in a multicentric cohort. METHODS: Between 2013 and 2019, patients scheduled for ultrasound-guided prostate biopsy were prospectively enrolled at 11 Italian institutions. Demographic, clinical and histological data were collected and analysed. Discrimination and calibration of Cormio nomogram were assessed with the receiver operator characteristics (ROC) curve and calibration plots. The clinical net benefit of the nomogram was assessed with decision curve analysis. Clinically significant PCa was defined as ISUP grade group > 1. RESULTS: After accounting for inclusion criteria, 1377 patients were analysed. 816/1377 (59%) had cancer at final pathology (574/816, 70%, clinically significant PCa). Multivariable analysis showed age, prostate volume, DRE and post-voided residual volume as independent predictors of any PCa. Discrimination of the nomogram for cancer was 0.70 on ROC analysis. Calibration of the nomogram was excellent (p = 0.94) and the nomogram presented a net benefit in the 40-80% range of probabilities. Multivariable analysis for predictors of clinically significant PCa found age, PSA, prostate volume and DRE as independent variables. Discrimination of the nomogram was 0.73. Calibration was poor (p = 0.001) and the nomogram presented a net benefit in the 25-75% range of probabilities. CONCLUSION: We confirmed that the Cormio nomogram can be used to predict the risk of PCa in patients at increased risk. Implementation of the nomogram in clinical practice will better define its role in the patient's counselling before prostate biopsy.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

External validation of a postoperative nomogram for the prediction of disease-specific survival in patients with papillary renal cell carcinoma using a large multicenter database.

PURPOSE: Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC). METHODS: A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied. RESULTS: The median follow-up was 38 months (IQR 11.8-80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60-0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77-0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20-80), but the median actual 5-year DSS in the same group was 58% (95% CI 52-65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%. CONCLUSIONS: The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.

Predictors of the Transition from Off to On Clamp Approach during Ongoing Robotic Partial Nephrectomy: Data from the CLOCK Randomized Clinical Trial.

PURPOSE: We sought to identify predictive factors of the transition from off clamp to on clamp robotic partial nephrectomy following an intraoperative decision. MATERIALS AND METHODS: In the multicenter, randomized, prospective CLOCK (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy) trial 152 and 149 of the 301 patients with a localized renal mass were assigned to undergo off clamp and on clamp robotic partial nephrectomy, respectively. Surgery was done at a total of 7 referral institutions by 1 surgeon per institution. A localized renal mass was defined as having a R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, location relative to polar lines, hilar) score less than 10. Surgeons had similar experience with at least 100 previous robotic partial nephrectomies. All patients underwent a preoperative and a 6-month renal scan. The current study deals with one of the secondary end points of the trial, comparing cases finalized as clampless (off robotic partial nephrectomy group) with those which were converted (shift robotic partial nephrectomy group). RESULTS: Of the 152 patients randomized to off clamp 61 (40%) were shifted to clamp with a median ischemia time of 15 minutes. In the shift robotic partial nephrectomy group the masses were larger (3.5 vs 2.2 cm) and more complex (R.E.N.A.L. score 7 vs 6). A significant association with transition was found for tumor diameter (OR 1.4) and the R.E.N.A.L. score continuously (OR 1.4) and when recoded in groups, including 4-no risk (referent OR 1), 5-6-low risk (OR 1.8), 7-8-intermediate risk (OR 3.6) and 9 or greater-high risk (OR 6.6). The shift robotic partial nephrectomy group had longer operative time, higher blood loss and increased performance of 2-layer renorrhaphy. No significant differences were noted in postoperative complications or renal function after 6 months. CONCLUSIONS: The transition from off to on clamp robotic partial nephrectomy is associated with renal mass diameter and complexity. Under the specific conditions of the current trial no harm was related to this decision.