External validation of a nomogram for outcome prediction in management of medium-sized (1-2 cm) kidney stones.

BACKGROUND: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations. METHODS: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan). RESULTS: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis. CONCLUSIONS: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

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.

Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy ­ which is used to reduce male sex hormone levels in prostate cancer patients ­ can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis.

BACKGROUND: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. METHODS: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. RESULTS: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. CONCLUSION: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

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.

External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study.

OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

Genitourinary manifestations of Lynch syndrome in the urological practice.

Objective: Lynch syndrome (LS) is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene. From a clinical perspective, LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general population. We aimed to provide a comprehensive overview of all the genitourinary manifestations of LS, focusing on incidence, diagnosis, clinical features, therapeutic strategies, and screening protocols. Methods: Previous literature was assessed through Medline, Scopus, and Google Scholar databases. A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was provided. Results: In the LS tumor spectrum, upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy, and the first most common cancer in the urological field, with an approximately 14-fold increased risk of developing UTUC compared to general population. LS diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process, including (i) clinical criteria, (ii) molecular testing, and (iii) genetic testing to confirm the hereditary disorder. The current European Association of Urology (EAU) guidelines recommend to perform molecular testing among UTUC patients under 65 years old, or UTUC patients with personal history of LS-related tumor, or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor, or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of onset. Newly diagnosed LS patients should be referred to a multidisciplinary management, including gastroenterologists and gynecologists. Finally, considering the increased risk of metachronous recurrence, treatments other than radical nephroureterectomy may be a valuable therapeutic alternative. Whether urological malignancies other than UTUC should be included in the LS tumor spectrum is still controversial. Conclusion: Considering the strict association between UTUC and LS, we believe that the urologist should recognize patients at increased risk for hereditary disease according to current EAU clinical criteria and address them to a comprehensive diagnostic algorithm, including molecular evaluation and genetic testing. To date, literature lacks clear evidence regarding the role of LS in developing bladder cancer, prostate cancer, or renal cell carcinoma, and current data are still inconclusive, highlighting the urgent need for further studies.

Effect of Degarelix Administration on Bone Health in Prostate Cancer Patients Without Bone Metastases. The Blade Study.

CONTEXT: As patients are now living with prostate cancer for longer, the long-term impact of hormonal treatment on bone health is an increasingly debated subject. OBJECTIVE: To characterize the changes in bone mineral density (BMD) and bone turnover markers after degarelix administration in prostate cancer patients without bone metastases. To explore the predictive role of body composition on treatment induced bone loss. METHODS: BMD and body composition (lean body mass, fat body mass, and appendicular mass index [ALMI]) were assessed by dual X-ray absorptiometry on study entry and after 12 months of degarelix therapy. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline, and 6 and 12 months. RESULTS: Twenty-nine patients entered the study. Degarelix administration was associated with a significant decrease in BMD after 12 months (2.4% reduction from baseline at lumbar spine). Serum CTX and ALP increased significantly (median increase from baseline 99% and 19.3%, respectively). An inverse correlation was observed between ALMI and CTX, but not ALP, at both baseline (Pearson r = -0.62, P < .0001) and month 12 (Pearson r = -0.41, P = .032). Moreover, a significant inverse correlation between changes in ALMI and CTX at 12 months (Pearson r = -0.43, P = .019) and a direct relationship between changes of ALMI and ALP (Pearson r = 0.44, P = .016) during degarelix therapy were observed. CONCLUSION: Degarelix administration is associated with a significant decrease in BMD and increase in bone turnover markers. ALMI is a promising predictor of bone loss in prostate cancer patients receiving androgen deprivation therapy, and ALMI changes during therapy are associated with bone turnover derangement favoring bone quality alterations.

Micropapillary bladder cancer: an evolving biology.

PURPOSE OF REVIEW: To summarize a comprehensive overview of more recent evidence on micropapillary bladder cancer (MPBC), focusing on actual incidence, clinical features, therapeutic strategies, and prognosis. RECENT FINDINGS: MPBC generally exhibits an aggressive behaviour compared with pure urothelial carcinoma (pUC) with advances in tumour stage and nodal and distant spread at diagnosis. Due to its rarity and presence of only small sample size and retrospective studies, no consensus currently exists regarding the most effective therapeutic strategy to be performed among nonmuscle-invasive (conservative treatment versus immediate radical cystectomy) and muscle-invasive MPBC (neoadjuvant therapy versus upfront radical cystectomy versus adjuvant chemotherapy). SUMMARY: The incidence of MPBC is recently increased according to latter literature, ranging from 2.9 to 7.6% of all bladder cancer. Despite its aggressive behaviour at time of presentation, more recent evidence fails to demonstrate a significant association between MPBC and worse outcomes compared with pUC when adjusted for clinical and pathological features. According to latter evidence, MPBC pathological response to NAC appears to be unsatisfactory compared with pUC patients while neoadjuvant immunotherapy with Pembrolizumab may represent an effective treatment among MPBC patients, based on PD-L1 and TMB expression.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Selecting the Best Candidates for Cisplatin-based Adjuvant Chemotherapy After Radical Cystectomy Among Patients with pN+ Bladder Cancer.

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p < 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal.

Oncologic Surveillance After Radical Nephroureterectomy for High-risk Upper Tract Urothelial Carcinoma.

BACKGROUND: The appropriate surveillance protocol after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is still poorly addressed. OBJECTIVE: To evaluate the appropriate intensity and duration of oncologic surveillance following RNU, according to a prior history of bladder cancer (BCa). DESIGN, SETTING, AND PARTICIPANTS: We identified 1378 high-risk UTUC patients, according to the European Association of Urology (EAU) guidelines, from a prospectively maintained database involving eight European referral centers. Surveillance protocol was based on cystoscopies and cross-sectional imaging, as per the EAU guidelines. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, we evaluated the noncumulative risk of bladder and other-site recurrences (including distant metastasis and locoregional relapse) against the follow-up time points, as suggested by the current EAU guidelines. Second, in an effort to identify the time points when the risk of other-cause mortality (OCM) exceeded that of recurrence and follow-up might be discontinued, we relied on adjusted Weibull regression. RESULTS AND LIMITATIONS: The median follow-up was 4 yr. A total of 427 and 951 patients with and without a prior BCa history, respectively, were considered. At 5-yr, the time point after which cystoscopies should be performed semiannually, the bladder recurrence risk was 10%; at 4 yr, the bladder recurrence risk was 13%. At 2 yr, the time point after which imaging should be obtained semiannually, the nonbladder recurrence risk was 42% in case of nonprior BCa and 47% in case of prior BCa; at 4 yr, the nonbladder recurrence risk was 23%. Among patients without a prior BCa history, individuals younger than 60 yr should continue both cystoscopies and imaging beyond 10 yr from RNU, 70-79-yr-old patients should continue only imaging beyond 10 yr, while patients older than 80 yr might discontinue oncologic surveillance because of an increased risk of OCM. Limitations include the fact that patients were treated and surveilled over a relatively long period of time. CONCLUSIONS: We suggest intensifying the frequency of imaging to semiannual till the 4th year after RNU, the time point after which the risk of recurrence was almost halved. Cystoscopies could be obtained annually from the 4th year given a similar risk of recurrence at 4 and 5 yr after RNU. Oncologic surveillance could be discontinued in some cases in the absence of a prior BCa history. PATIENT SUMMARY: In this study, we propose a revision of the current guidelines regarding surveillance protocols following radical nephroureterectomy. We also evaluated whether oncologic surveillance for high-risk upper tract urothelial carcinoma could be discontinued and, if so, in what circumstances.

Robot-Assisted, Laparoscopic, and Open Radical Cystectomy: Pre-Operative Data of 1400 Patients From The Italian Radical Cystectomy Registry.

Introduction: The Italian Radical Cystectomy Registry (RIC) is an observational prospective study aiming to understand clinical variables and patient characteristics associated with short- and long-term outcomes among bladder cancer (BC) patients undergoing radical cystectomy (RC). Moreover, it compares the effectiveness of three RC techniques - open, robotic, and laparoscopic. Methods: From 2017 to 2020, 1400 patients were enrolled at one of the 28 centers across Italy. Patient characteristics, as well as preoperative, postoperative, and follow-up (3, 6, 12, and 24 months) clinical variables and outcomes were collected. Results: Preoperatively, it was found that patients undergoing robotic procedures were younger (p<.001) and more likely to have undergone preoperative neoadjuvant chemotherapy (p<.001) and BCG instillation (p<.001). Hypertension was the most common comorbidity among all patients (55%), and overall, patients undergoing open and laparoscopic RC had a higher Charlson Comorbidities Index (CCI) compared to robotic RC (p<.001). Finally, laparoscopic patients had a lower G-stage classification (p=.003) and open patients had a higher ASA score (p<.001). Conclusion: The present study summarizes the characteristic of patients included in the RIC. Future results will provide invaluable information about outcomes among BC patients undergoing RC. This will inform physicians about the best techniques and course of care based on patient clinical factors and characteristics.

Metastasis Within Three Years from Radical Nephroureterectomy as a Potential Surrogate for Overall Survival.

INTRODUCTION: The only phase III trial that evaluated the role of adjuvant chemotherapy following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) was terminated early. Thus, eventual overall survival (OS) surrogacy, as per Prentice, cannot be assessed in this setting. We aimed to identify an intermediate clinical endpoint (ICE) that could serve as an OS surrogate after RNU for UTUC. PATIENTS AND METHODS: We retrospectively analyzed 823 high-grade UTUC patients treated with RNU at 8 tertiary referral centers. We explored the role of any recurrence (aR), defined as recurrence in the urinary tract or in the resection bed as well the presence of distant metastasis (DM), defined as metastatic disease outside the urinary tract and regional lymph nodes, on OS through a time-varying Cox regression analyses fitted at the landmark points of 1, 2, 3, and 4 years from RNU. Models' discrimination was assessed using Harrell's c index, after internal validation. RESULTS: Median follow-up for survivors was 5.6 years (interquartile range: 2.0-8.8). Overall, 391 and 212 patients experienced aR and DM, respectively. In a time-varying model, aR and DM were predictors of OS: hazard ratio [HR]:1.20, 95% confidence interval [CI]: 1.13-1.28 (P < .001) and HR:1.26, 95% CI: 1.18-1.34 (P < .001), respectively. Progression to DM within 3 years from RNU was the most informative ICE for predicting OS (c index: 0.81; HR: 4.40; 95%CI: 2.45-7.92; P < .001), compared to DM within 1, 2, and 4 years (c indexes: 0.74, 0.76, and 0.78, respectively). Progression to DM within 3 years from RNU was further found superior for predicting OS compared to aR at any landmark points. CONCLUSIONS: Progression to DM within 3 years represents a potential OS surrogate for surgically-treated UTUC. This information could help in patient counseling, future study design and expedite results release of ongoing randomized controlled trials.

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.

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.

Diagnostic accuracy of preoperative lymph node staging of bladder cancer according to different lymph node locations: A multicenter cohort from the European Association of Urology - Young Academic Urologists.

BACKGROUND: The preoperative lymph node (LN) staging of bladder cancer (BCa) addresses the subsequent therapeutic strategy and influences patient's prognosis. However, sparce evidence exists regarding the accuracy of conventional cross-sectional imaging, such as computed tomography or magnetic resonance imaging, in correctly detect LN status. We aimed to assess the diagnostic accuracy of conventional cross-sectional imaging in detecting preoperative LN involvement among BCa patients treated with radical cystectomy and pelvic lymph node dissection. METHODS: We retrospectively analyzed data of 1,104 patients who underwent preoperative LN staging with computed tomography or magnetic resonance imaging and subsequent radical cystectomy with pelvic lymph node dissection for BCa between 1997 and 2017 at three tertiary referral centers. Patients receiving neoadjuvant chemotherapy were excluded. We assessed the concordance between clinical (cN) and pathological LN (pN) status, defined as the accuracy of imaging in detecting LN involvement using pathological specimen as reference; concordance was expressed according to Cohen's kappa coefficient. Location-based sub-analyses were performed, distinguishing among external iliac, intern iliac, obturator, common iliac, presacral and paraaortic LNs. RESULTS: Among 870 cN0 patients, 68.9% were confirmed pN0 at pathological report; while among 234 cN+ patients, 50.5% were found with LN metastases at pathological specimen. Overall, conventional imaging showed slight concordance (64.9%) between cN and pN stages (sensitivity: 30%; specificity: 84%). At sub-analysis, no agreement between cN and pN status was found in each LN location, with the only exception of common iliac LNs with slight concordance (37.5%). Common iliac LNs achieved the highest sensitivity and positive likelihood ratio (15% and 2.4, respectively) compared to other LN locations. CONCLUSIONS: Overall, preoperative cross-sectional imaging exhibited a slight concordance between cN and pN status. Our location-based sub-analyses showed unsatisfactory results in each LN location- Thus, nomograms combining morphological patterns with serological and clinicopathological features are urgently required.

The Role of Prior Bladder Cancer on Recurrence in Patients Treated with Radical Nephroureterectomy.

INTRODUCTION: The prognostic role of prior history of bladder cancer (BCa) among patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is poorly addressed. We aimed to investigate the role of prior BCa on any recurrence, distant metastases, and bladder recurrence following RNU among low-grade (LG) and high-grade (HG) UTUC patients. PATIENTS AND METHODS: We retrospectively analyzed 1,580 UTUC patients treated with RNU at 8 tertiary referral centers between 1992 and 2016. Any recurrence was defined as recurrence in the urinary tract, in the resection bed, or distant metastases (defined as disease outside the urinary tract and regional lymph nodes). Time to recurrence was computed from RNU. Multivariable Cox models were generated to predict risk of any recurrence, distant metastases, and bladder recurrence according to prior BCa history, coded as no prior BCa, non-muscle-invasive (NMIBC), and muscle-invasive BCa (MIBC). RESULTS: Median follow-up for survivors was 4 years. Overall, 71%, 25%, and 4% of patients had no prior BCa, NMIBC and MIBC. 5-year any recurrence-free survival was 61%, 41%, and 19% in LG (P < .001) and 42%, 34%, and 30% in HG patients (P = .1) with no prior BCa, NMIBC, and MIBC. On multivariable models, LG patients with NMIBC and MIBC showed a significantly higher risk of any recurrence compared to no prior BCa (both p≤0.005); previous NMIBC was associated with any recurrence among HG patients (P = 0.04). 5-year distant metastases-free survival was 92%, 90%, and 87% in LG (P > .05) and 68%, 75%, and 45% in HG patients (P = .01) with no prior BCa, NMIBC, and MIBC. Previous NMIBC increased the risk of bladder recurrence among LG (P < .001) and HG (P = .003) patients. CONCLUSIONS: UTUC patients with prior history of BCa exhibit a higher risk of any recurrence after RNU. Our study provides important information which could address patient's counseling and decision-making process.

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.