Open versus robotic partial nephrectomy in obese patients: a multi-institutional propensity score-matched analysis (UroCCR 43-Robese study).

INTRODUCTION: There is limited evidence on the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN) in obese patients (BMI ≥ 30 kg/m2). In this study, we aimed to compare perioperative and oncological outcomes of RPN and OPN. METHODS: We relied on data from patients who underwent PN from 2009 to 2017 at 16 departments of urology participating in the UroCCR network, which were collected prospectively. In an effort to adjust for potential confounders, a propensity-score matching was performed. Perioperative outcomes were compared between OPN and RPN patients. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Overall, 1277 obese patients (932 robotic and 345 open were included. After propensity score matching, 166 OPN and 166 RPN individuals were considered for the study purposes; no statistically significant difference among baseline demographic or tumor-specific characteristics was present. A higher overall complication rate and major complications rate were recorded in the OPN group (37 vs. 25%, p = 0.01 and 21 vs. 10%, p = 0.007; respectively). The length of stay was also significantly longer in the OPN group, before and after propensity-score matching (p < 0.001). There were no significant differences in Warm ischemia time (p = 0.66), absolute change in eGFR (p = 0.45) and positive surgical margins (p = 0.12). At a median postoperative follow-up period of 24 (8-40) months, DFS and OS were similar in the two groups (all p > 0.05). CONCLUSIONS: In this study, RPN was associated with better perioperative outcomes (improvement of major complications rate and LOS) than OPN. The oncological outcomes were found to be similar between the two approaches.

Chatbots vs andrologists: Testing 25 clinical cases.

OBJECTIVE: AI-derived language models are booming, and their place in medicine is undefined. The aim of our study is to compare responses to andrology clinical cases, between chatbots and andrologists, to assess the reliability of these technologies. MATERIAL AND METHOD: We analyzed the responses of 32 experts, 18 residents and three chatbots (ChatGPT v3.5, v4 and Bard) to 25 andrology clinical cases. Responses were assessed on a Likert scale ranging from 0 to 2 for each question (0-false response or no response; 1-partially correct response, 2- correct response), on the basis of the latest national or, in the absence of such, international recommendations. We compared the averages obtained for all cases by the different groups. RESULTS: Experts obtained a higher mean score (m=11/12.4 σ=1.4) than ChatGPT v4 (m=10.7/12.4 σ=2.2, p=0.6475), ChatGPT v3.5 (m=9.5/12.4 σ=2.1, p=0.0062) and Bard (m=7.2/12.4 σ=3.3, p<0.0001). Residents obtained a mean score (m=9.4/12.4 σ=1.7) higher than Bard (m=7.2/12.4 σ=3.3, p=0.0053) but lower than ChatGPT v3.5 (m=9.5/12.4 σ=2.1, p=0.8393) and v4 (m=10.7/12.4 σ=2.2, p=0.0183) and experts (m=11.0/12.4 σ=1.4,p=0.0009). ChatGPT v4 performance (m=10.7 σ=2.2) was better than ChatGPT v3.5 (m=9.5, σ=2.1, p=0.0476) and Bard performance (m=7.2 σ=3.3, p<0.0001). CONCLUSION: The use of chatbots in medicine could be relevant. More studies are needed to integrate them into clinical practice.

Radical Prostatectomy for Nonmetastatic Prostate Cancer in Renal Transplant Recipients: Outcomes for a Large Contemporary Cohort and a Matched Comparison to Patients Without a Transplant.

BACKGROUND AND OBJECTIVE: It is unknown whether renal transplant receipt (RTR) status can affect perioperative and oncological outcomes of radical prostatectomy (RP). Our aim was to evaluate oncological and functional outcomes of RTR patients treated with RP for cN0M0 prostate cancer (PCa) via comparison with a no-RTR cohort. METHODS: RTR patients who had undergone RP at seven European institutions during 2001-2022 were identified. A multi-institutional cohort of no-RTR patients treated with RP during 2004-2022 served as the comparator group. Propensity score matching (PSM) at a ratio of 1:4 was used to match no-RTR patients to the RTR cohort according to age, prostate-specific antigen, and final pathology features. We used Kaplan-Meier plots and multivariable Cox, logistic, and Poisson log-linear regression models to test the outcomes of interest. KEY FINDINGS AND LIMITATIONS: After PSM, we analyzed data for 102 RTR and 408 no-RTR patients. RTR patients experienced higher estimated blood loss (EBL), longer length of hospital stay (LOS) and time to catheter removal, higher postoperative complication rates, and a lower continence recovery rate (all p < 0.001). On multivariable analyses, RTR independently predicted unfavorable operative time (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.18-1.25), LOS (OR 1.57, 95% CI 1.32-1.86), EBL (OR 2.24, 95% CI 2.18-2.30), and time to catheter removal (OR 1.93, 95% CI 1.68-2.21), but not complications or continence recovery. There were no significant differences for any oncological outcomes (biochemical recurrence, local or systemic progression) between the RTR and no-RTR groups. While no PCa deaths were recorded, the overall mortality rate was significantly higher in the RTR group (17% vs 0.5%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although RP is feasible for RTR patients, the procedure poses non-negligible surgical challenges, with longer operative time and LOS and higher EBL, but no major differences in terms of complications and continence recovery. The RTR group had similar oncological outcomes to the no-RTR group but significantly higher overall mortality related to causes other than PCa. Therefore, careful selection for RP is required among candidates with previous RTR. PATIENT SUMMARY: Removal of the prostate for prostate cancer is possible in patients who have had a kidney transplant, and cancer control outcomes are comparable to those for the general population. However, transplant patients have a higher risk of death from causes other than prostate cancer and the prostate surgery is likely to be more challenging.

Gain of Chromosome 5q Predicts a Favorable Prognosis in Localized Renal Cell Carcinoma.

Approximately 65% of renal cell carcinomas (RCC) are diagnosed at a localized stage. We investigated the chromosome 5q gain impact on disease-free survival (DFS) in RCC patients. Overall, 676 patients with stages 1-2 RCC and having cytogenetic analysis were included. Gain of 5q was observed in 108 patients, more frequently in clear cell (ccRCC) than non-clear cell tumors. Gain of 5q is likely an independent prognostic factor since the concerned patients had a decreased recurrence risk in stages 1-2 RCC, confirmed in multivariable analysis. Detecting 5q gain could enhance recurrence risk assessment, allowing tailored post-surgery surveillance, and reducing unnecessary treatments.

Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Is CIS a Contraindication to Hyperthermic Intravesical Chemotherapy (HIVEC) after BCG-Failure?

CIS of the bladder is associated with a high risk of progression. In the case of BCG failure, radical cystectomy should be performed. For patients who refuse or are ineligible, bladder-sparing alternatives are evaluated. This study aims to investigate the efficacy of Hyperthermic IntraVesical Chemotherapy (HIVEC) depending on the presence or absence of CIS. This retrospective, multicenter study was conducted between 2016 and 2021. Patients with non-muscle-invasive bladder cancer (NMIBC) with BCG failure received 6-8 adjuvant instillations of HIVEC. The co-primary endpoints were recurrence-free survival (RFS) and progression-free survival (PFS). A total of 116 consecutive patients met our inclusion criteria of whom 36 had concomitant CIS. The 2-year RFS rate was 19.9% and 43.7% in patients with and without CIS, respectively (p = 0.52). Fifteen patients (12.9%) experienced progression to muscle-invasive bladder cancer with no significant difference between patients with and without CIS (2-year PFS rate = 71.8% vs. 88.8%, p = 0.32). In multivariate analysis, CIS was not a significant prognostic factor in terms of recurrence or progression. In conclusion, CIS may not be considered a contraindication to HIVEC, as there is no significant association between CIS and the risk of progression or recurrence after treatment.

Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure.

PURPOSE: To evaluate hyperthermic intravesical chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette-Guérin (BCG) therapy. METHODS: This is a multicenter retrospective series from a national database (7 expert centers). Between January 2016 and October 2021, patients treated with HIVEC for NMIBC who failed BCG have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. RESULTS: A total of 116 patients treated with HIVEC and with a follow-up > 6 months were included in this study and retrospectively analyzed. The median follow-up was 20.6 months. The 12 month-RFS (recurrence-free survival) rate was 62.9%. The bladder preservation rate was 87.1%. Fifteen patients (12.9%) progressed to muscle infiltration, three of them having a metastatic disease at the time of progression. Predictive factors of progression were T1 stage, high grade and very high-risk tumors according to the EORTC classification. CONCLUSION: Chemohyperthermia using HIVEC achieved an RFS rate of 62.9% at 1 year and enabled a bladder preservation rate of 87.1%. However, the risk of progression to muscle-invasive disease is not negligible, particularly for patients with very high-risk tumors. In these patients who fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression.

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).

OBJECTIVES: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. MATERIALS AND METHODS: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours. RESULTS: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). CONCLUSIONS: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.

Partial nephrectomy in solitary kidneys: comparison between open surgery and robotic-assisted laparoscopy on perioperative and functional outcomes (UroCCR-54 study).

PURPOSE: The management of solitary kidney tumors is a surgical challenge, requiring irreproachable results on both oncological and functional outcomes. The goal of our study was to compare the perioperative results of robotic-assisted partial nephrectomy (RAPN) to open surgery in this indication. METHODS: We led a multicentric study based on the prospectively maintained French national database UroCCR. Patients who underwent partial nephrectomy on a solitary kidney between 1988 and 2020 were included. Clinical and pathological data were retrospectively analyzed. The main outcome of the study was the analysis of the variation of the estimated glomerular filtration rate (eGFR) calculated according to MDRD at 3, 6, 12, and 24 months depending on the chosen surgical approach. The secondary outcomes were the comparison of Trifecta success, perioperative complications, and length of hospital stay. RESULTS: In total, 150 patients were included; 68 (45%) in the RAPN group and 82 (55%) in the open surgery group. The two groups were comparable for all data. The variation of eGFR at 3, 6, 12, or 24 months was comparable without any significant difference between the 2 groups (p = 0.45). Trifecta was achieved in 40% of the patients in the RAPN group and 33% in the open group (p = 0.42). A significant difference was observed for the length of stay, 5 days for the robot group versus 9 days for the open surgery group (p < 0.0001). CONCLUSION: In our study, the surgical approach did not modify functional results and we noted a significant decrease in hospital stay and complications in the RAPN group. RAPN is a safe and efficient method for management of kidney tumors in solitary kidneys.

Who Is at Risk of Death after Renal Trauma? An Analysis of Thirty-Day Mortality after 1,799 Cases of Renal Trauma.

INTRODUCTION: The aim of the study was to report the 30-day mortality (30DM) after renal trauma and identify the risk factors associated with death. METHODS: The TRAUMAFUF project was a retrospective multi-institutional study including all patients with renal trauma admitted to 17 French hospitals between 2005 and 2015. The included population focused on patients of all age groups who underwent renal trauma during the study period. The primary outcome was death within 30 days following trauma. The multivariate logistic regression model with a stepwise backward elimination was used to identify predictive factors of 30DM. RESULTS: Data on 1,799 renal trauma were recorded over the 10-year period. There were 59 deaths within 30 days of renal trauma, conferring a 30DM rate of 3.27%. Renal trauma was directly involved in 5 deaths (8.5% of all deaths, 0.3% of all renal trauma). Multivariate stepwise logistic regression analysis revealed that age >40 years (odds ratio [OR] 2.18; 95% confidence interval [CI]: 1.20-3.99; p = 0.01), hemodynamic instability (OR 4.67; 95% CI: 2.49-9; p < 0.001), anemia (OR 3.89; 95% CI: 1.94-8.37; p < 0.001), bilateral renal trauma (OR 6.77; 95% CI: 2.83-15.61; p < 0.001), arterial contrast extravasation (OR 2.09; 95% CI: 1.09-3.96; p = 0.02), and concomitant visceral and bone injuries (OR 6.57; 95% CI: 2.41-23.14; p < 0.001) were independent predictors of 30DM. CONCLUSION: Our large multi-institutional study supports that the 30DM of 3.27% after renal trauma is due to the high degree of associated injuries and was rarely a consequence of renal trauma alone. Age >40 years, hemodynamic instability, anemia, bilateral renal trauma, arterial contrast extravasation, and concomitant visceral and bone lesions were predictors of death. These results can help clinicians to identify high-risk patients.

Evaluation of oncological outcomes of robotic partial nephrectomy according to the type of hilar control approach (On-clamp vs Off-clamp), a multicentric study of the French network of research on kidney cancer-UROCCR 58-NCT03293563.

PURPOSE: To compare off-clamp vs on-clamp robotic partial nephrectomy (RPN) for renal cell carcinoma (RCC) in terms of oncological outcomes, and to assess the impact of surgical experience (SE). METHODS: We extracted data of a contemporary cohort of 1359 patients from the prospectively maintained database of the French national network of research on kidney cancer (UROCCR). The primary objective was to assess the positive surgical margin (PSM) rate. We also evaluated the oncological outcomes regardless of the surgical experience (SE) by dividing patients into three groups of SE as a secondary endpoints. SE was defined by the caseload of RPN per surgeon per year. For the continuous variables, we used Mann-Whitney and Student tests. We assessed survival analysis according to hilar control approach by Kaplan-Meier curves with log rank tests. A logistic regression multivariate analysis was used to evaluate the independent factors of PSM. RESULTS: Outcomes of 224 off-clamp RPN for RCC were compared to 1135 on-clamp RPN. PSM rate was not statistically different, with 5.6% in the off-clamp group, and 11% in the on-clamp group (p = 0.1). When assessing survival analysis for overall survival (OS), local recurrence-free survival (LR), and metastasis-free survival (MFS) according to hilar clamping approach, there were no statistically significant differences between the two groups with p value log rank = 0.2, 0.8, 0.1, respectively. In multivariate analysis assessing SE, hilar control approach, hospital volume (HV), RENAL score, gender, Age, ECOG, EBL, BMI, and indication of NSS, age at surgery was associated with PSM (odds ratio [OR] 1.03 (95% CI 1.00-1.04), 0.02), whereas SE, HV, and type of hilar control approach were not predictive factors of PSM. CONCLUSION: Hilar control approach seems to have no impact on PSM of RPN for RCC. Our findings were consistent with randomized trials.

Predictive factors of recurrence after surgery in patients with non-metastatic renal cell carcinoma with venous tumor thrombus (UroCCR-56 Study).

PURPOSE: To assess the oncological outcomes of renal cell carcinoma (RCC) associated with tumor thrombus and identify predictive factors of recurrence. METHODS: Multi-institutional study that included patients with cT3-4N0-1M0 RCC with tumoral thrombus identified in the prospective UroCCR database (CNIL DR 2013-206; NCT03293563). pT3a without involvement of the renal vein were excluded. All patients underwent radical nephrectomy and a thrombectomy of the renal vein ± inferior vena cava ± right atrium. The primary endpoint was recurrence-free survival (RFS). Thirty-two patients who had adjuvant therapies (tyrosine kinase inhibitors or mTOR inhibitor) were compared to control group (surveillance) in a propensity score-matched 1:1 sub-analysis RESULTS: A total of 432 patients were included: 70.4% pT3a, 20.1% pT3b, 4.2% pT3c and 5.3% pT4. Tumor characteristics were: 90.7% clear cell RCC, 13.9% pN1, and 87.1% high Fuhrman grade. 173 patients (40%) had disease recurrence, and median RFS was 37.3 months (95% CI, 26.4-46.7). In a multivariate analysis (Cox model), predictive factors of recurrence were: pT4 (HR 2.66; 95% CI, 1.42-4.99; p = 0.002), pN1 (HR 2.53; 95% CI, 1.46-4.39; p < 0.001), tumor necrosis (HR 2.92; 95% CI, 1.85-4.62; p < 0.001), tumor size > 10 cm (HR 1.56; 95% CI, 1.08-2.24; p = 0.018). Adjuvant therapy was a protective factor of cancer recurrence (HR 0.33; 95% CI, 0.17-0.66; p = 0.002). Propensity score-matched sub-analysis of adjuvant vs control (surveillance) confirmed adjuvant treatment as a protective factor of cancer recurrence (Log rank p = 0.015). CONCLUSIONS: In this contemporary multi-institutional cohort of RCC + tumor thrombus, we reported higher recurrence rate shortly after surgical excision and demonstrated an oncological benefit of adjuvant treatment.

Oncological Outcomes of Distal Ureterectomy for High-Risk Urothelial Carcinoma: A Multicenter Study by The French Bladder Cancer Committee.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon disease and its gold-standard treatment is radical nephroureterectomy (RNU). Distal ureterectomy (DU) might be an alternative for tumors of the distal ureter but its indications remain unclear. Here, we aimed to evaluate the oncological outcomes of DU for UTUC of the pelvic ureter. We performed a multicenter retrospective analysis of patients with UTUC who underwent DU. The primary endpoint was 5-year cancer-specific survival (CSS), followed by overall survival (OS), intravesical recurrence-free (IVR) and homolateral urinary tract recurrence-free (HUR) survivals as secondary endpoints. Univariate and multivariate Cox regressions were performed to assess factors associated with outcomes. 155 patients were included, 91% of which were high-risk. 5-year CSS was 84.4%, OS was 71.9%, IVR-free survival was 43.6% and HUR-free survival was 74.4%. Multifocality, high grade and tumor size were the most significant predictors of survival endpoints. Of note, neither hydronephrosis nor pre-operative diagnostic ureteroscopy/JJ stent were associated with any of the endpoints. Perioperative morbidity was minimal. In conclusion, DU stands as a possible alternative to RNU for UTUC of the pelvic ureter. Close monitoring is mandatory due to the high risk of recurrence in the remaining urinary tract.

The Role of CT in the Staging and Follow-Up of Testicular Tumors: Baseline, Recurrence and Pitfalls.

Ultrasound imaging of the testis represents the standard-of-care initial imaging for the diagnosis of TGCT, whereas computed tomography (CT) plays an integral role in the initial accurate disease staging (organ-confined, regional lymph nodes, or sites of distant metastases), in monitoring the response to therapy in patients who initially present with non-confined disease, in planning surgical approaches for residual masses, in conducting follow-up surveillance and in determining the extent of recurrence in patients who relapse after treatment completion. CT imaging has also an important place in diagnosing complications of treatments. The aims of this article are to review these different roles of CT in primary TGCT and focus on different pitfalls that radiologists need to be aware of.

Ultrasound and Magnetic Resonance Imaging of Burned-Out Testicular Tumours: The Diagnostic Keys Based on 48 Cases.

The spontaneous regression of testicular germ-cell tumours is a rare event whose mechanisms have yet to be elucidated. In the majority of published cases, tumour regression is concomitant with the metastatic development of the disease. Residual lesions, often referred to as burned-out testicular tumours (BOTTs), are difficult to diagnose due to the paucity of published data, especially in the field of imaging. The aim of this article is to describe the radiological signs of BOTTs on multimodal ultrasound and multiparametric MRI from a series of 48 patients whose diagnosis was confirmed histologically. The demographic, clinical and laboratory characteristics of the patients are studied, as well as the data of the imaging examinations, including conventional scrotal ultrasound, shear-wave elastography, contrast-enhanced ultrasound (CEUS) and multiparametric MRI. A total of 27 out of 48 patients were referred for investigation of primary testicular lesion following the discovery of retroperitoneal metastases, 18/48 patients were referred because of lesions suspected on an ultrasound that was performed for an infertility work-up, and 3/48 were referred because of scrotal clinical signs. Of these last 21 patients (infertility work-up/scrotal clinical sign), 6 were found to be metastatic on the extension work-up. Of the 48 orchiectomy specimens, tumour involution was complete in 41 cases, and a small active contingent remained in 7 cases, with 6 suspected upon advanced US and MRI. Typically, BOTTs appear on a conventional ultrasound as ill-delineated, hypoechoic and hypovascular nodular areas. Clustered microliths (60.4%) and macrocalcifications (35.4%) were frequent. Shear-wave elastography showed areas of focal induration (13.5 ± 8.4 vs. 2.7 ± 1.2 kPa for normal parenchyma, p < 0.01) in 92.5% of the patients for whom it was performed, and contrast ultrasonography demonstrated hypoperfusion of these lesions. Of the 42 MRIs performed, BOTTs corresponded to nodules on T2-weighted sequences (hyposignal) with significantly increased ADC values compared with healthy parenchyma (2 ± 0.3 versus 1.3 ± 0.3 × 10−3 mm2/s, p < 0.01) and an enhancement defect after injection. This enhancement defect overlapped the lesions visible on T2-weighted sequences in most cases. In the case of predominant partial regression, an enhanced portion after contrast injection was visible on MRI in all seven patients of our series, and in six of them a focal diffusion restriction zone was also present. Spontaneously involuted testicular germ-cell tumours have specific radiological signs, and all of the mentioned examinations contribute to this difficult diagnosis, even histologically, because there is no tumour cell left. These signs are similar whether the patient is initially symptomatic metastatic or whether the discovery is fortuitous on the occasion of an infertility work-up, and whatever the seminomatous or non-seminomatous nature of the germ-cell tumour, when this can be determined. The appearance of regressed germ-cell tumours is often trivialized, which can lead to the wrong diagnosis of an extra gonadal germ-cell tumour (in metastatic patients) or of scarring from an acute event such as trauma or infection, which is not recognized or forgotten. In our series, two patients had an unrecognized diagnosis in their history, with local and/or distant recurrence. An improvement in diagnosing burned-out tumours, combining advanced US and MRI, is necessary in order to optimize patient management, with special attention paid to asymptomatic patients, to prompt extension screening and orchiectomy with analysis of the whole testis. This may reveal a persistent viable tumour or lesions of germinal neoplasia in situ, which are precursors of testicular germ-cell tumours.

Leydig Cell Tumors of the Testis: An Update of the Imaging Characteristics of a Not So Rare Lesion.

Pre-operative testicular tumor characterization is a challenge for radiologists and urologists. New data concerning imaging approaches or immunochemistry markers improve the management of patients presenting with a testicular tumor, sometimes avoiding radical orchiectomy. In the past 20 years, imaging modalities, especially ultrasound (US) and magnetic resonance imaging (MRI), improved, allowing for great progress in lesion characterization. Leydig cell tumors (LCT) are rare testicular tumors developing from the stromal tissue, with relatively scarce literature, as most of the studies focus on the much more frequent germ cell tumors. However, with the increase in testicular sonography numbers, the incidence of LCT appears much higher than expected, with some studies reporting up to 22% of small testicular nodules. Multimodal ultrasound using Doppler, Elastography, or injection of contrast media can provide crucial arguments to differentiate LCT from germ cell tumors. Multiparametric MRI is a second intention exam, but it allows for extraction of quantifiable data to assess the diagnosis of LCT. The aims of this article are to review the latest data regarding LCT imaging features, using multimodal ultrasound and multiparametric MRI, and to focus on the peculiar aspect of the testis of patients with Klinefelter's syndrome. The possibility of an LCT should be raised in front of a small hypoechoic tumor with a marked corbelling hypervascularization in an otherwise normal testicular pulp. Ultrasonographic modules, such as ultrasensitive Doppler, contrast-enhanced ultrasonography, or elastography, can be used to reinforce the suspicion of LCT. MRI provides objective data regarding vascularization and enhancement kinetics.

Escherichia coli-Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer.

Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale. SIGNIFICANCE: In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli-specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies. This article is highlighted in the In This Issue feature, p. 2221.

Pathological and genetic markers improve recurrence prognostication with the University of California Los Angeles Integrated Staging System for patients with clear cell renal cell carcinoma.

PURPOSE: To elucidate which patients with clear cell renal cell carcinoma have the highest risk for disease relapse after curative nephrectomy is challenging but is acutely relevant in the era of approved adjuvant therapies. Pathological and genetic markers were used to improve the University of California Los Angeles Integrated Staging System (UISS) for the risk stratification and prognostication of recurrence free survival (RFS). PATIENTS AND METHODS: Necrosis, sarcomatoid features, Rhabdoid features, chromosomal loss 9p, combined chromosomal loss 3p14q and microvascular invasion (MVI) were tested in univariable and multivariable analyses for their ability to improve the discriminatory ability of the UISS. RESULTS: In the development cohort, during the median follow-up time of 43.4 months (±SD 54.1 months), 50/240 (21%) patients developed disease recurrence. MVI (HR: 2.22; p = 0.013) and the combined loss of chromosome 3p/14q (HR: 2.89; p = 0.004) demonstrated independent association with RFS and were used to improve the assignment to the UISS risk category. In the current UISS high-risk group, only 7/50 (14%) recurrence cases were correctly identified; while in the improved system, 23/50 (45%) were correctly prognosticated. The concordance index meaningfully improved from 0.55 to 0.68 to distinguish patients at intermediate risk versus high risk. Internal validation demonstrated a robust prognostication of RFS. In the external validation cohort, there was no case with disease recurrence in the low-risk group, and the mean RFS times were 13.2 (±1.8) and 8.2 (±0.8) years in the intermediate and high-risk groups, respectively. CONCLUSIONS: Adding MVI and combined chromosomal loss3p/14q to the UISS improves the ability to define the patient group with clear cell renal cell carcinomawho are at the highest risk for disease relapse after surgical treatment.

Impact of Hospital Volume on the Outcomes of Renal Trauma Management.

BACKGROUND: Some health care systems have set up referral trauma centers to centralize expertise to improve trauma management. There is scant and controversial evidence regarding the impact of provider's volume on the outcomes of trauma management. OBJECTIVE: To evaluate the impact of hospital volume on the outcomes of renal trauma management in a European health care system. DESIGN SETTING AND PARTICIPANTS: A retrospective multicenter study, including all patients admitted for renal trauma in 17 French hospitals between 2005 and 2015, was conducted. INTERVENTION: Nephrectomy, angioembolization, or nonoperative management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four quartiles according to the caseload per year: low volume (eight or fewer per year), moderate volume (nine to 13 per year), high volume (14-25/yr), and very high volume (≥26/yr). The primary endpoint was failure of nonoperative management defined as any interventional radiology or surgical procedure needed within the first 30 d after admission. RESULTS AND LIMITATIONS: Of 1771 patients with renal trauma, 1704 were included. Nonoperative management was more prevalent in the very-high- and low-volume centers (p = 0.02). In a univariate analysis, very high hospital volume was associated with a lower risk of nonoperative management failure than low (odds ratio [OR] = 0.54; p = 0.05) and moderate (OR = 0.48; p = 0.02) hospital volume. There were fewer nephrectomies in the high- and very-high-volume groups (p = 0.003). In a multivariate analysis, very high volume remained associated with a lower risk of nonoperative management failure than low (OR = 0.48; p = 0.04) and moderate (OR = 0.42; p = 0.01) volume. Study limitations include all the shortcomings inherent to its retrospective multicenter design. CONCLUSIONS: In this multicenter study, management of renal trauma varied according to hospital volume. There were lower rates of nephrectomy and failure of nonoperative management in very-high-volume centers. These results raise the question of centralizing the management of renal trauma, which is currently not the case in our health care system. PATIENT SUMMARY: In this study, management of renal trauma varied according to hospital volume. Very-high-volume centers had lower rates of nephrectomy and failure of nonoperative management.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study.

BACKGROUND: The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately. OBJECTIVE: To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naïve PCa. DESIGN, SETTING, AND PARTICIPANTS: We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial (NCT03368547). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used. RESULTS AND LIMITATIONS: A total of 168 patients with treatment-naïve IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8-24.6)ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT-positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET. CONCLUSIONS: PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naïve IR and HR PCa. PATIENT SUMMARY: We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.