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.

Efficacy and tolerance of hyperthermic intravesical chemotherapy (HIVEC) according to the number of instillations administered.

PURPOSE: To report the oncological outcomes and the tolerance between 6 instillations and more than 6 cycles of hyperthermic intravesical chemotherapy(HIVEC) in patients with non-muscle invasive bladder cancer(NMIBC). METHODS: This is a multicenter retrospective study from a national database including 9 expert centers. All patients treated with HIVEC between 2016 and 2023 for NMIBC were included. Patients were classified into two groups according to the total number of HIVEC instillations, including induction plus maintenance. Kaplan-Meier curves were computed to present survival outcomes. RESULTS: 261 patients with a median follow-up of 25.5 months were included. 199(76.2%) and 62(23.8%) were treated by 6 and more than 6 cycles of HIVEC, respectively. The 2-years RFS(40.2% vs. 34.4%,p = 0.3) and the 2-years PFS(86% vs. 87%,p = 0.85) were similar between group treated with 6 and more than 6 instillations. 2-years CSS and OS were also similar between both groups. Univariate Cox regression showed no association between the number of bladder instillation and RFS (HR = 1.2 95%CI[0.8-1.84], p = 0.3) or PFS (HR = 0.8 95%CI[0.29-2.02], p = 0.2). In the group treated with more than 6 cycles, 2-years RFS and 2-years PFS were similar between patients who received induction plus maintenance compared to those treated with induction only. Finally, hematuria and urinary burning were significantly higher in the group treated by more than 6 cycles (21% vs. 8.5%(p < 0.01),and 29% vs. 17% (p = 0.03), respectively). Serious side effects(grade ≥ 3) are rare(3.1%) and similar in both groups. CONCLUSIONS: Results show no significant difference in two years RFS, PFS, CSS and OS according to number of instillations received, while toxicity profile seems better in the group receiving six instillations only.

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.

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.

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.

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.

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.

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.

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.

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.