Impact of positive vascular margins status after surgical resection of non-metastatic renal cell carcinoma with caval tumour thrombus: a propensity score multicentre study.

BACKGROUND: Data evaluating the impact of positive vascular margins (PVMs) following surgical resection of non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus are lacking. OBJECTIVE: To analyze the oncological impact of positive vascular margins following surgical resection of RCC with IVC tumor thrombus. METHODS: Patients who underwent radical nephrectomy with the removal of IVC tumour thrombus for RCC between 2000 and 2019 were included. PVMs were identified from pathology reports defined as microscopically identified tumour present in the IVC wall at the site of resection or in case of thrombus was not completely removed. To achieve balance in baseline characteristics between patients with PVMs versus negative vascular margins, we used inverse probability of treatment weighting (IPTW) based on the propensity score. Local recurrence, distant metastasis and overall mortality were evaluated between groups using Cox proportional hazards regression models. RESULTS: 209 patients were analyzed. Among them, 49 (23%) patients with PVMs were identified. Median follow-up was 55 months. After adjustment, excellent balance was achieved for most propensity score variables. In IPTW analysis, PVMs was associated with a higher risk of local recurrence (HR = 3.66; p < 0.001) without any impact on systemic recurrence (HR = 1.15; p = 0.47) or overall mortality (HR = 1.23; p = 0.48). Limitations include the sample size and unmeasured confounding. CONCLUSION: Our results suggest that a PVMs in patients with RCC after nephrectomy with thrombectomy is associated with a higher risk of local recurrence, however, it did not appear to influence the risk of distant metastasis or death.

Successful Reuse of Kidney Graft After Early Recurrence of Primary Focal and Segmental Glomerulosclerosis.

Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine+corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer: a multicenter, randomized, non-comparative, phase II study (Oncodistinct 004 - AURA trial).

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies. METHODS AND ANALYSIS: Oncodistinct 004 - AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety. ETHICS AND DISSEMINATION: The study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03674424).

Low-risk prostate cancer selected for active surveillance with negative MRI at entry: can repeat biopsies at 1 year be avoided? A pilot study.

PURPOSE: In patients considered for active surveillance (AS), the use of MRI and targeted biopsies (TB) at entry challenges the approach of routine "per protocol" repeat systematic biopsies (SB) at 1 year. This pilot study aimed to assess whether an approach of performing repeat biopsies only if PSA kinetics are abnormal would be safe and sufficient to detect progression. METHODS: Prospective single-centre study of 149 patients on AS with low-risk PCa, a negative MRI at entry, followed for a minimum of 12 months between 01/2007 and 12/2015. Group 1 (n = 78) patients had per-protocol 12-month repeat SB; group 2 (n = 71) patients did not. Surveillance tests for tumour progression were for both groups: for cause SB and MRI-TB biopsies if PSA velocity (PSA-V) > 0.75 ng/ml/year, or PSA doubling time (PSADT) < 3 years. The main objectives are to compare the 2-year rates of tumour progression and AS discontinuation between groups. The secondary objectives are to estimate the diagnostic power of PSA-V and PSA-DT, to predict the risk of tumour progression. RESULTS: Overall, 21 out of 149 patients (14.1%) showed tumour progression, 17.1% for group 1 and 12.3% for group 2, and 31 (21.2%) discontinued AS at 2 years. There was no difference between the 2 groups (p = 0.56). The area under the PSA-V and PSADT curves to predict tumour progression was 0.92 and 0.83, respectively. CONCLUSIONS: We did not find any significant difference for progression and AS discontinuation rate between the 2 groups. The PSA kinetic seems accurate as a marker of tumour progression. These results support the conduct of a multi-centre prospective trial to confirm these findings.

Incidence, clinicopathological features and fusion transcript landscape of translocation renal cell carcinomas.

AIMS: Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney tumour characterized by translocations involving the transcription factor TFE3 or TFEB. tRCC was introduced into the World Health Organization classification in 2004, but much is still unknown about the natural history, clinicopathological features and outcomes of the disease. The aim of this study was to describe the landscape of fusion transcript in a large single-institution series of fluorescence in-situ hybridization (FISH)-confirmed tRCCs and then to compare it to morphological and clinical data. METHODS AND RESULTS: Paired-end RNA sequencing was performed within a prospective database of the Department of Pathology, Centre Hospitalier Régional Universitaire (Lille, France). The diagnosis of tRCC was confirmed by FISH. Among a total of 1130 identified renal cell carcinomas, 21 cases (1.9%) showed rearrangement of the TFE3 (n = 20) or (TFEB) (n = 1) gene. Median patient age was 31 years (range = 15-47), and the female-to-male ratio was 6:1. Five different TFE3 fusion transcripts were identified; the most frequent TFE3 partners were PRCC (n = 4) and SFPQ (n = 4). The other partners involved were ASPCR1 (n = 1) and MED15 (n = 1) genes as well as a novel TFE3 partner, GRIPAP1. CONCLUSIONS: We identified a new fusion partner, GRIPAP1. The prognostic role of transcript type could not be determined because our number of cases was too small. Four patients (19%) died of the disease, all of which presented with a lymph node involvement at diagnosis. We confirm that tRCC can be an aggressive tumour, especially those of advanced clinical stage.

Clear cell papillary renal cell carcinoma is an indolent and low-grade neoplasm with overexpression of cyclin-D1.

AIMS: Several entities have been individualized recently within the family of renal neoplasms with papillary features. Clear cell papillary renal cell carcinoma (CCPRCC) was first described in patients with end-stage renal disease, but is also observed in patients with normal renal function. The objective of this study was to document the clinicopathological and immunohistochemical characteristics of CCPRCC, with a special emphasis on cyclin D1 expression. METHODS AND RESULTS: The patients were 25 men and 17 women, mean age 60.7 years. Seventeen patients had a chronic renal disease. All tumours were stage pT1, with a mean diameter of 2 cm. Six tumours were multifocal. Tumours cells were mainly cuboidal, with clear cytoplasm and low-grade nuclei apically aligned. In all cases, Fuhrman nuclear grade was one or two. No necrosis or vascular invasion was seen. During follow-up (10-72 months), no metastasis or death related to the disease was observed. Immunohistochemistry showed strong and diffuse cytokeratin 7 immunoreactivity in all cases, but no labelling for AMACR or TFE3. There was diffuse nuclear cyclin D1 immunoreactivity in 83% of cases. CONCLUSION: CCPRCC is now a well-characterized entity. This tumour is an indolent and very low-grade neoplasm. Here we report the first study, to our knowledge, demonstrating the overexpression of cyclin D1 immunostaining by this tumour.

Standard of care for adult Wilms tumor? From adult urologist to pediatric oncologist. A retrospective review.

Nephroblastoma or Wilms tumor, a common embryonal tumor in children, can occasionally occur in adults. The survival of patients older than 18 years is reported to be significantly inferior to that of pediatric patients. Establishing a diagnosis for these rare tumors can be challenging for both clinicians and pathologists, who are not accustomed to considering Wilms tumor as a potential differential in adults. This leads to misdiagnosis and a subsequent delay in the initiation of appropriate therapy. The standard of care is not well established for Wilms tumors in adults. We provide here a comprehensive review of the international literature on the subject with the current management protocols in France. We also propose the need of strong inter-disciplinary collaboration between surgeons, pathologists, and medical and pediatric oncologists for increasing knowledge and formulating treatment strategies for these rare tumors. Homogenous guidelines for treating adults with Wilms tumors have been proposed for all patients in France.

Active surveillance for non-muscle invasive bladder cancer.

Most of low grade (LG) bladder tumors will experience disease recurrence and very few of them (<2%) will experience disease progression. Therefore active surveillance (AS) for LG non-muscle invasive bladder cancer (NMIBC) has emerged. The goal of our study was to provide a literature review of AS for LG NMIBC including inclusion criteria, modalities and oncological outcomes. We conducted a systematic review (registered in PROSPERO: CRD42018102935) using MEDLINE and EMBASE between June 2018 and August 2018 with the following terms: LG, NMIBC, AS, urothelial neoplasm. Overall, 6 studies that reached our scope of review were included cumulating 403 patients with 2 prospective trials. Inclusion criteria were: recurrent LG (G1 and G2) Ta or T1 NMIBC, with a negative cytology, a low volume (<10 mm) and low number (<5) of tumors. Cystoscopy every 3 months during the first 2 years and every 6 months afterwards were required. AS dropout criteria were presence of tumor-related symptoms, a positive cytology, a modification of tumor morphology or size and patient's request. Pooled data showed an overall 65% reclassification rate where 15% of patients were reclassified based on grade and 10% on stage with a median follow-up of 32 months (IQR, 24-42 months). Only one study reported on progression to MIBC in 4 patients out of 186 (2%). Most of patients enrolled in an AS protocol for recurrent LG NMIBC will undergo a TURBT eventually. Many patients may be eligible to this therapeutic approach but current knowledge does not support its use in daily practice outside of a clinical trial.

Contemporary best practice in the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer.

BACKGROUND: We aimed to provide a comprehensive literature review on the best practice management of patients with nonmetastatic muscle-invasive bladder cancer (MIBC) using neoadjuvant chemotherapy (NAC). METHOD: Between July and September 2018, we conducted a systematic review using MEDLINE and EMBASE electronic bibliographic databases. The search strategy included the following terms: Neoadjuvant Therapy and Urinary Bladder Neoplasms. RESULTS: There is no benefit of a single-agent platinum-based chemotherapy. Platinum-based NAC is the gold standard therapy and mainly consists of a combination of cisplatin, vinblastine, methotrexate, doxorubicin, gemcitabine or even epirubicin (MVAC). At 5 years, the absolute overall survival benefit of MVAC was 5% and the absolute disease-free survival was improved by 9%. This effect was observed independently of the type of local treatment and did not vary between subgroups of patients. Moreover, a ypT0 stage (complete pathological response) after radical cystectomy was a surrogate marker for improved oncological outcomes. High-density MVAC has been shown to decrease toxicity (with a grade 3-4 toxicity ranging from 0% to 26%) without impacting oncological outcomes. To date, there is no role for carboplatin administration in the neoadjuvant setting in patients that are unfit for cisplatin-based NAC administration. So far, there is no published trial evaluating the role of immunotherapy in a neoadjuvant setting, but many promising studies are ongoing. CONCLUSION: There is a strong level of evidence supporting the clinical use of a high-dose-intensity combination of methotrexate, vinblastine, doxorubicin and cisplatin in a neoadjuvant setting. The landscape of MIBC therapies should evolve in the near future with emerging immunotherapies.

Prognostic value of combined p53 and survivin in pT1G3 urothelial carcinoma of the bladder.

pT1G3 bladder tumors have a high tendency to recur and progress. We evaluated the prognostic values of the depth of submucosal invasion and immunostaining with survivin and p53 in 30 pT1G3 urothelial carcinomas at the first endoscopic resection. The depth of invasion was evaluated toward the muscularis mucosa and measured using a micrometer. Survivin and p53 immunostaining were performed using an automated immunostainer. Of the patients, 19 (63%) had tumor recurrence, 11 (37%) had tumor progression, 10 (33%) had metastatic spread, and 10 (33%) died of the disease. Infiltration of deep lamina propria (pT1b) and a micrometric measure of 1.5 mm or more were associated with an increased risk of tumor local and/or metastatic progression (P = .03 and P = .02, respectively). A combined high expression of survivin (

[Primary neuroectodermal tumour of the kidney invading the wall of the inferior vena cava. Surgical strategy]. / Tumeur neuro-ectodermique primitive du rein envahissant la paroi de la veine cave inférieure: stratégie chirurgicale.

Primary neuroectodermal tumours (PNET) are very aggressive malignant tumours, rapidly progressing to metastasis and death. They rarely involve the kidney, as only 23 cases have been described in the literature. Renal tumours, regardless of their histology, spread to the inferior vena cava (IVC) in 4% to 10% of cases. Invasion of the inferior vena cava wall by tumour thrombus is rare and, when it occurs, is often limited to the ostium of the renal vein. The authors report a case of primary neuroectodermal tumour of the kidney with thrombus in the inferior vena cava ascending to the right atrium (level IV), invading the wall of the IVC and associated with a non-infiltrating papillary urothelial tumour of the ureter. They describe the surgical management of this tumour and present a review of the literature.

[Urachal cancers]. / Les cancers de l'ouraque.

Urachal cancer is a rare pathology (less than 1% among all bladder tumors) with a poor prognosis for all stages, because of clinical delay leading to a late diagnosis, difficult differential diagnosis with bladder cancer, and no consensus for the treatment, mostly about the chemotherapy for advanced stages, because there are no data from prospective studies. A surgical treatment can be performed for the localized stages, but there are no real guidelines for local relapses and metastatic progression treatment. Those cancers are not radio- or chemosensitive; nevertheless data from fundamental research are missing. As this pathology is really uncommon, there are no clinical studies with targeted therapies. The purpose of this review is to introduce the most important clinical and paraclinical features of those cancers, and the usual treatment performed.

Results of endoluminal occlusion of the inferior vena cava during radical nephrectomy and thrombectomy.

BACKGROUND: The surgical management of renal tumours with thrombi in the inferior vena cava (IVC) has become the gold standard treatment. OBJECTIVE: To evaluate endoluminal occlusion of the IVC during radical nephrectomy with either retrohepatic (level II) or suprahepatic (level III) caval tumour thrombus. DESIGN, SETTING, AND PARTICIPANTS: From January 2000 to October 2007, 28 consecutive patients with renal cell carcinoma presenting a thrombus level II or III were treated with endoluminal occlusion of the free IVC cranial. SURGICAL PROCEDURE: The occlusion balloon was positioned under transesophageal echography (TEE) control through a cavotomy performed at the level of the renal vein ostium. Thrombectomy and radical nephrectomy were then performed. MEASUREMENTS: Operative time, perioperative bleeding, and pre- and postoperative complications were assessed. Overall patient survival time, disease-free survival, and development of metastasis were assessed. RESULTS AND LIMITATIONS: Caval thrombectomy was performed successfully in all patients. IVC replacement with an expanded polytetrafluoroethylene graft or patch closure after lateral cavectomy was performed in 10 and 4 patients, respectively. Average operative time was 160 min (range: 120-210). There was no perioperative mortality. The complications were one splenectomy and one early thrombosis of the IVC. Mean length of follow-up was 22.1 mo (range: 3-90). There was no local or IVC tumour recurrence. Cause-specific death and metastasis occurred in six (21.4%) and nine patients (32.1%), respectively. Thirteen patients (46.4%) are disease-free. CONCLUSIONS: Endoluminal occlusion of the IVC with TEE monitoring for level II and III thrombus avoided a suprahepatic or subdiaphragmatic approach of the IVC. Segmental resection and reconstruction of the IVC could also be performed in case of adherent thrombi.

Testicular natural killer T-cell lymphoma.

Primary testicular lymphomas account for less than 5% of all testicular neoplasms. Testicular natural killer (NK)/T-cell lymphomas are exceptional and have a very poor prognosis. We report the case of a 30-year-old French Caucasian man with testicular NK/T-cell lymphoma of the following immunophenotype: CD2+, CD3epsilon+ and CD56+. Despite intensive chemotherapy, the disease progressed rapidly, with death occurring 2 months after diagnosis.