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Objective: Bladder cancer (BC) is considered one of the malignancies with moderate-high incidence, high rate of recurrence and costly management. Diagnosis and staging are thus important for therapeutic purposes. Considering the risk of residual tumour and understaging, in specific cases, international guidelines recommend performing a second transurethral resection of the bladder (reTURB). Our study aimed to evaluate the impact of hexaminolevulinate Photodynamic Diagnostics (PDD) at first TURB on the rate of residual tumour. Materials and Methods: We retrospectively analysed patients undergoing TURB in our centre between 2012 and 2020. Eightytwo patients had a re-TURB after a first complete TURB with a delay < 3 months. Patients who had an incomplete first resection were excluded. We compared patients who underwent standard white light cystoscopy/TURB and then hexaminolevulinate PDDguided reTURB (group A, n = 49) and patients with PDD-cystoscopy/ TURB at the first procedure then white light cystoscopy/reTURB (group B, n = 33). The residual tumour rate at reTURB as well as median recurrence-free survival (RFS) were compared between the two groups. Results: Residual tumour at reTURB was detected in 48.8% of cases in our cohort, with a significant difference between the two groups (71.4% in group A versus 12.5% in group B, p < 0.001). After a median follow-up of 22 months, the median RFS was 15 months in Group A and 32 months in Group B, but this difference was not significant (p = 0.7). Conclusions: Using PDD at the time of the initial TURB had a statistically significant impact on the rate of residual tumour at the reTURB. Nevertheless, the percentage of residual tumour even with the use of PDD does not allow for safely omitting second resection. Performing a reTURB with PDD for patients who did not have it initially, provides the same benefit in terms of recurrence-free survival.

Introduction: Digestive metastases (DMs) from renal cell cancer (RCC) are rare. Over the past decade, the overall survival of metastatic RCC (mRCC) has been improved by tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors. The main objective of this study was to assess the incidence of metastases of the digestive tract in this new field of treatment. The secondary objectives were to evaluate the clinical characteristics, prognosis, treatments used for DMs, and median time between the diagnosis of RCC or mRCC and DMs.Materials and Methods: A retrospective analysis of data collected from all patients with mRCC between 2007 (the time of TKI was a standard of care) and 2019 was carried out at the Paoli-Calmettes Institute (Marseille, France). Computer research software using artificial intelligence (ConSoRe®) was used to identify patients and assess their characteristics.Results: Between January 2007 and December 2019, 11 out of 660 (1.6%) mRCC patients had metastases of the gastrointestinal tract. The median age was 62 years. Of the 11 patients, 81.8% experienced digestive bleeding or anemia. Only 2 patients were asymptomatic. The metastases were mainly duodenal (50%) and gastric (41.6%). The median time from cancer diagnosis and from metastatic disease to gastrointestinal metastasis was 4.3 years (3 months−19.2 years) and 2.25 years (0 days−10.2 years), respectively. Local treatment was performed in 38.5% of cases by endoscopy (60%), surgery (20%) and radiotherapy (40%) with success rates of 33, 100, and 50%, respectively. Etiological treatment was modified following the discovery of DM in 84.6% of the cases. The median survival was 1 year from the diagnosis of DM (13 days−9.4 years). Two patients were still alive 2.9 and 9.4 years after the diagnosis of DM.Conclusion: This is the largest monocentric retrospective analysis of DM in patients with RCC. It seems to be a rare and late event in the course of the disease. Local treatment combined with systemic treatment could improve survival. In the context of prolonged survival with the new based immunotherapy treatments in mRCC, we suggest that unexplained anemia or persistent digestive symptoms could be explored by endoscopy.

Background: Renal cell carcinoma is the third most prevalent urological cancer worldwide and about 30% of patients present with metastatic disease at the time of diagnosis. Systemic treatments for metastatic renal cell carcinoma have improved recently. Vascular endothelial growth factor targeting therapies were the previous standard of care. However, immune checkpoint inhibitors used in second line therapy have now been shown to improve patient survival. We report a case of metastatic renal cell carcinoma with nivolumab as a second-line therapy after progression with tyrosine kinase inhibitor therapy. Unusual adverse events in metastatic renal cell carcinoma, such as vitiligo, were observed in this patient who developed a remarkable documented pathological complete response to his renal tumor.Case presentation: A 60-year-old caucasian male was diagnosed with a pulmonary metastatic clear cell renal cell carcinoma. Sunitinib was used as first line treatment without success. He received nivolumab in second-line treatment. He developed several immune-related adverse events, most notably vitiligo. The patient had a radiological complete response on metastatic sites, with a significant decrease of renal tumor volume and underwent cytoreductive nephrectomy after 2 years of treatment, confirming the pathological complete response. The patient remains disease-free for 10 months without further systemic therapy after nivolumab discontinuation.Conclusions: Pathological complete response with nivolumab in metastatic renal cell carcinoma is rare. This case further highlights the potentially predictive role of immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma and raises questions concerning the role of nephrectomy after immune checkpoint inhibitor therapy. Further studies are needed to better identify predictive factors for treatment response to immunotherapy in metastatic renal cell carcinoma, and to better understand the role of nephrectomy after nivolumab treatment.

The CDKN2B-AS1 gene, also called ANRIL, is located at the human CDKN2A/B locus at 9p21.3 and transcribed by RNA polymerase II into a long non-coding RNA of 3834 bp. The CDKN2B-AS1 gene overlaps a critical region of 125 kb covering the CDKN2B gene. The CDKN2A/B locus encompasses three major tumor suppressors juxtaposed and joined into a p16-CDKN2A/p15-CDKN2B/p14-ARF gene cluster. CDKN2A encodes splice variants p16-CDKN2A and p14-ARF, and CDKN2B encodes p15-CDKN2B. ANRIL shares a bidirectional promoter with the p14-ARF gene and is transcribed from the opposite strand to the cluster. We performed an analysis of the expression level of ANRIL and tumor suppressor p16-CDKN2A, p15-CDKN2B, and p14-ARF genes using quantitative RT-PCR in a multitumor panel. We observed the overexpression of the four genes ANRIL, p16-CDKN2A, p15-CDKN2B, and p14-ARF in the great majority of the 17 different cancer types. ANRIL was upregulated in 13/17 tumors compared to normal tissues, ranging from 5% (prostate cancer) to 91% (cervix cancer), with variable expression of p16-CDKN2A, p15-CDKN2B, and p14-ARF genes. A high positive correlation was identified between levels of expression of ANRIL and the three tumor suppressors. The strongest positive association was observed with p14-ARF (p < 0.001) in all but one (lung squamous cell carcinoma) of the examined tumor types. This correlation suggests coordinated deregulated mechanisms in all cancer types through aberrant activation of a bidirectional p14-ARF/ANRIL promoter. Furthermore, significant positive correlation was unexpectedly established in prostatic carcinomas, in contradiction with previous data.

Background and objective: Data regarding open conversion (OC) during minimally invasive surgery (MIS) for renal tumors are reported from big databases, without precise description of the reason and management of OC. The objective of this study was to describe the rate, reasons, and perioperative outcomes of OC in a cohort of patients who underwent MIS for renal tumor initially. The secondary objective was to find the factors associated with OC. Methods: Between 2008 and 2022, of the 8566 patients included in the UroCCR project prospective database (NCT03293563), who underwent laparoscopic or robot-assisted minimally invasive partial (MIPN) or radical (MIRN) nephrectomy, 163 experienced OC. Each center was contacted to enlighten the context of OC: “emergency OC” implied an immediate life-threatening situation not reasonably manageable with MIS, otherwise “elective OC”. To evaluate the predictive factors of OC, a 2:1 paired cohort on the UroCCR database was used. Key findings and limitations: The incidence rate of OC was 1.9% for all cases of MIS, 2.9% for MIRN, and 1.4% for MIPN. OC procedures were mostly elective (82.2%). The main reason for OC was a failure to progress due to anatomical difficulties (42.9%). Five patients (3.1%) died within 90 d after surgery. Increased body mass index (BMI; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01–1.09, p = 0.009) and cT stage (OR: 2.22, 95% CI: 1.24–4.25, p = 0.008) were independent predictive factors of OC. Conclusions and clinical implications: In MIS for renal tumors, OC was a rare event (1.9%), caused by various situations, leading to impaired perioperative outcomes. Emergency OC occurred once every 300 procedures. Increased BMI and cT stage were independent predictive factors of OC. Patient summary: The incidence rate of open conversion (OC) in minimally invasive surgery for renal tumors is low. Only 20% of OC procedures occur in case of emergency, and others are caused by various situations. Increased body mass index and cT stage were independent predictive factors of OC.

Abstract Renal cell carcinoma (RCC) is most often diagnosed at a localized stage, where surgery is the standard of care. Existing prognostic scores provide moderate predictive performance, leading to challenges in establishing follow-up recommendations after surgery and in selecting patients who could benefit from adjuvant therapy. In this study, we developed a model for individual postoperative disease-free survival (DFS) prediction using machine learning (ML) on real-world prospective data. Using the French kidney cancer research network database, UroCCR, we analyzed a cohort of surgically treated RCC patients. Participating sites were randomly assigned to either the training or testing cohort, and several ML models were trained on the training dataset. The predictive performance of the best ML model was then evaluated on the test dataset and compared with the usual risk scores. In total, 3372 patients were included, with a median follow-up of 30 months. The best results in predicting DFS were achieved using Cox PH models that included 24 variables, resulting in an iAUC of 0.81 [IC95% 0.77–0.85]. The ML model surpassed the predictive performance of the most commonly used risk scores while handling incomplete data in predictors. Lastly, patients were stratified into four prognostic groups with good discrimination (iAUC = 0.79 [IC95% 0.74–0.83]). Our study suggests that applying ML to real-world prospective data from patients undergoing surgery for localized or locally advanced RCC can provide accurate individual DFS prediction, outperforming traditional prognostic scores.

Abstract Robot-assisted partial nephrectomy (RAPN) is the standard of care for small, localized kidney tumors. This surgery is conducted within a short hospital stay and can even be performed as outpatient surgery in selected patients. In order to allow early rehabilitation of patients, an optimal control of postoperative pain is necessary. High-pressure pneumoperitoneum during surgery seems to be the source of significant pain during the first hours postoperatively. Our study is a prospective, randomized, multicenter, controlled study which aims to compare post-operative pain at 24 h between patients undergoing RAPN at low insufflation pressure (7 mmHg) and those operated on at standard pressure (12 mmHg) using the AirSeal system. This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT05404685).

Liposarcoma of the spermatic cord (LSC) is a very rare disease. In literature, are reported less than 350 cases. Genitourinary sarcomas account for

Abstract Active surveillance (AS) is a standard treatment option for low risk localized prostate cancer. However, the risk of anxiety and depression compared to other curative strategies, namely radical prostatectomy (RP) and radiotherapy (RT), is controversial. This study consisted in a French representative sample of 4174 5-years cancer survivors. Self-reported data, including quality-of-life assessment, were prospectively collected through telephone interviews. Among the 447 survivors with PC, we selected 292 patients with localized prostate cancer, T1–T2 stage, Gleason score ≤ 7 and we compared anxiety and depressive symptoms according to treatment strategy. Among patients on AS, 14.9% received curative treatment during the 5 years of follow-up. Anxiety was reported in 34.3% of cases in the AS group versus 28.6% in the RP group and 31.6% in the RT group (p = 0.400), while depressive symptoms were reported in 14.9% of cases in the AS group versus 10.7% in the RP group and 22.8% in the RT group (p = 0.770). Consumption of anxiolytics reported did not vary significantly between the 3 groups (p = 0.330). In conclusion, patients managed with AS for localized prostate cancer do not report more anxiety or depressive symptoms than patients managed with curative treatment, encouraging the extended use of active surveillance.

Background: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected health care priorities. Objective: To explore and analyse trends in public online search for urological cancers. Design, setting, and participants: We performed a retrospective analysis using the Google Health Trends online tool. Data related to urological cancer terms (“prostate cancer”, “kidney cancer”, and “bladder cancer”) were extracted. We analysed trends for the whole world and for five countries: Italy, the UK, France, Sweden, and the USA. Outcome measurements and statistical analysis: A join-point regression model was used to define significant changes in trends over time. Week percentage changes (WPCs) were estimated to summarise linear trends. The Mann-Whitney test was used to compare the search volume during the COVID-19 pandemic period (from January 2020 to April 2021) and the equivalent period of 2018 and 2019. Results and limitations: During COVID-19, worldwide online interest decreased significantly for all urological cancers, especially prostate cancer (WPC: –13.9%, p = 0.004; WPC: –5.4%, p < 0.001; and WPC: –4.3%, p < 0.001, for prostate, kidney, and bladder cancers, respectively). The most important decline was observed in the USA. The interest for all cancers was significantly less during the COVID-19 pandemic than in the same periods of 2018 and 2019. Conclusions: Online interest in urological cancers decreased significantly during the COVID-19 pandemic. Future studies will tell us whether this will translate into worse oncological outcomes. Patient summary: Patients are increasingly searching the Internet to get information on cancer. We explored Google queries during the COVID-19 pandemic and found that online interest decreased significantly for all urological cancers, especially prostate cancer. We do not know yet whether this will translate into worse prognosis for patients.

BackgroundImmune checkpoint inhibitors deeply modified metastatic renal cell carcinoma’s management, and confront us to adverse events that we were not used to with conventional anti-cancer therapies. We report the case of a patient who received nivolumab as second-line treatment of a metastatic clear cell renal cell carcinoma and who developed bullous pemphigoid four years after nivolumab introduction, with persistent exacerbations even after its discontinuation.Case presentationA 66-year-old man was diagnosed with lung metastasis eight years after radical nephrectomy for a clear cell renal cell carcinoma. He firstly received an anti-angiogenic agent combination, and then received anti-programmed death 1 (PD1) nivolumab as second-line treatment. Nivolumab led to prolonged disease control, but after four years of exposure the patient developed skin lesions consistent with bullous pemphigoid. After seven years of nivolumab administration and perfect disease stability, nivolumab was discontinued and surveillance was proposed. Despite nivolumab discontinuation, the patient continued to develop bullous pemphigoid exacerbations. Metastatic renal cell carcinoma was still perfectly stable more than two years after immune checkpoint discontinuation with no further anti-cancer therapy.DiscussionWe report the case of a refractory bullous pemphigoid which occurred four years after nivolumab introduction and lasted despite nivolumab discontinuation, in a patient whose metastatic renal cell carcinoma is still controlled after more than two years without any anticancer treatment. This highlights the potential association between immune-related adverse events and response to immune checkpoint inhibitors, and underlines the occurrence of late-onset and long-lasting immune-related adverse events even after discontinuation of treatment, which must encourage us to remain vigilant in the long term.

Purpose To evaluate Hyperthermic-Intra-Vesical Chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with High-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who fail BCG therapy or are contraindicated to BCG. Methods Between June 2016 and October 2019, patients treated with HIVEC for mostly high-risk NMIBC who failed BCG or BCG-naive if BCG contraindicated have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. Results Fifty-three patients, median age 72 [39–93] years, were included in this study (n = 29 BCG-failure and n = 24 BCG-naive). The median follow-up was 18 months. The bladder preservation rate was 92.4%. The 12 months-RFS rate was 60.5%. The RFS rates for BCG-naive and BCG-failure groups were respectively 70% and 52.2% at 12 months. Three patients progressed to muscle infiltration, all in the BCG-failure group and all in the very high-risk EORTC group. Two of them developed metastatic disease and died from bladder cancer. Conclusion Chemohyperthermia using HIVEC achieved a RFS rate of 60% at 1 year and enabled a bladder preservation rate of 92%. Given the low risk of progression in the BCG-naive group, HIVEC could be a good alternative. Conversely, for patients with very high-risk tumors that 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 to muscle-invasive disease.

Abstract Background To assess the prognostic value of the extent of positive surgical margins (PSM) following radical prostatectomy (RP) on biochemical recurrence (BR) with long-term follow-up. Methods This retrospective study analyzed 1275 RPs performed between January 1992 and December 2013 in two university centers in Marseille (France). The inclusion criteria were: follow-up > 24 months, undetectable postoperative prostate-specific antigen (PSA), no seminal vesicle (SV) invasion, no lymph node invasion confirmed by surgery (pN0) or imaging (pNx), and no neoadjuvant or adjuvant treatment. BR was defined by PSA level ≥ 0.2 ng/mL on two successive samples. We included 189 patients, divided into two groups: - Focal PSM (fPSM): single PSM (sPSM) ≤3 mm; - Extensive PSM (ePSM): sPSM with linear length > 3 mm or several margins regardless of the length. Results The median follow-up was 101 months (18–283) and the median age was 63 years (46–76). BR occurred in only 12.1% (14/115) of cases involving fPSM and in 54.1% (40/74) of cases involving ePSM. In the multivariate model, ePSM patients were significantly associated with increased BR compared to fPSM (hazard ratio [HR] = 6.11; 95% confidence interval [CI] = 3.25–11.49). The ePSM significantly decreased BR-free survival (p

The development of immune checkpoint inhibitors (ICI) has dramatically changed the landscape of therapies for metastatic renal cell carcinoma. However, many patients do not benefit from such therapy and prognostic or predictive validated biomarker validated for ICI are still needed to better select and treat patient. Plasmatic soluble immune checkpoints have been described as potential immune biomarkers in hematological malignancies and solids tumors, then, we would like to explore the prognostic value of different soluble immune checkpoints in patients with mRCC treated with nivolumab after TKI. We prospectively collected plasma samples before nivolumab infusion from 38 patients previously treated for mRCC with TKI at Paoli-Calmettes Institute, from the NIVOREN GETUG-AFU 26 study (NCT03013335). Enzyme-linked immunosorbent assays (ELISA) were performed for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3A1 and BTN2A1. Among the different soluble checkpoints analyzed, only high baseline plasmatic level of BTN2A1 was significantly associated with shorter PFS: median PFS was 3.95 months for sBTN2A1high vs 14.30 months for sBTN2A1low (sBTN2A1 cut-off: 6.7ng/mL; HR = 2.26, 95%CI [0.68 – 4.60], p = 0.0307). There was no statistical difference in OS between sBTN2A1high and sBTN2A1low. Our results suggest that the baseline level of plasmatic BTN2A1 could be an independent prognosis factor of PFS after nivolumab for pre-treated patient with mRCC. However, these results need to be validated in a larger prospective cohort and the biological role of BTN subfamily and γδ T cell immunity in mRCC must be elucidated.

Although immune checkpoint inhibitors have shown improvement in survival in comparison to chemotherapy in urothelial bladder cancer, many patients still fail to respond to these treatments and actual efforts are made to identify predictive factors of response to immunotherapy. Understanding the tumor-intrinsic molecular basis, like oncogenic pathways conditioning the presence or absence of tumor-infiltrating T cells (TILs), should provide a new rationale for improved anti-tumor immune therapies. In this study, we found that urothelial bladder cancer from human samples bearing PIK3CA gene mutations was significantly associated with lower expression of a defined immune gene signature, compared to unmutated ones. We identified a reduced 10-gene immune gene signature that discriminates muscle-invasive bladder cancer (MIBC) samples according to immune infiltration and PIK3CA mutation. Using a humanized mouse model, we observed that BKM120, a pan-PI3K inhibitor, significantly inhibited the growth of a human bladder cancer cell line bearing a PIK3CA mutation, associated to increased immune cell infiltration (hCD45+). Using qRT-PCR, we also found an increase in the expression of chemokines and immune genes in PIK3CA-mutated tumors from mice treated with BKM120, reflecting an active immune infiltrate in comparison to untreated ones. Moreover, the addition of BKM120 rendered PIK3CA-mutated tumors sensitive to PD-1 blockade. Our results provide a relevant rationale for combination strategies of PI3K inhibitors with immune checkpoint inhibitors to overcome resistance to immune checkpoint inhibitors.

Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006. All patients signed an informed consent. Results of molecular analyses were coupled with survival analyses. Overall, 25 genes (75.8%) were significantly overexpressed in MIBC and 15 (45.5%) were deregulated in NMIBC as compared with normal tissue. On multivariate analysis, risk of NMIBC recurrence was increased with high FOXP3/CD8 ratio and overexpression of OX40L (p = 0.016 and p = 0.0039, respectively). In MIBC, a molecular signature of 3 genes (OX40L, CD8 and TIGIT) was significantly associated with prognosis in terms of recurrence-free and overall survival (p = 0.0007 and p = 0.007). RT-PCR findings were confirmed by immunohistochemistry for CD8 and FOXP3, with high association between mRNA and protein levels. Finally, risk of recurrence of non–muscle-invasive bladder cancer was increased with high FOXP3/CD8 ratio and OX40L overexpression. We identified a 3 gene molecular signature associated with prognosis of muscle-invasive bladder cancer. These results confirm the useful role of immune checkpoints in bladder carcinogenesis and suggest targets for therapy.

Encrusted uretero-pyelitis is a rare and serious disease, related to the presence of calcifications in the pelvicalyceal system and ureter, associated with chronic urinary tract infection. In most cases, the causal agent of this infection lithiasis is corynebacterium urealyticum. The specific aspect of calcifications on CT scan can help to suggest diagnosis. To avoid a delay in diagnosis (which is frequent), an accurate exploration by the bacteriologist is crucial. The combination of a glycopeptides antibiotherapy and urine acidification has proved its effectiveness, as described in the medical literature. We report the case of a 77-year-old male patient, successfully treated for a bilateral encrusted uretero-pyelitis by local acidification (Thomas's solution) followed by oral acidification (ammonium chloride).

Objective. The objective of this study was to compare perioperative, oncologic, and functional outcomes of TLPN (transperitoneal laparoscopic partial nephrectomy) versus RLPN (retroperitoneal). Patients and Methods. From 1997 to 2009, a retrospective study of 153 consecutive patients who underwent TLPN or RLPN for suspicious renal masses was performed. Complications, functional and oncological outcomes were compared between the 2 groups. Results. With a mean followup of 39 and 32 months, respectively, 66 and 87 patients had TLPN and RLPN, respectively. Tumor location was more often posterior in the RLPN and more often anterior in the TLPN. Mean operative time and mean hospital stay were longer in the TLPN group with 190±85 min versus 154±47 (𝑃=0.001) and 9.2±6.4 days versus 6.2±4.5 days (𝑃