French AFU Cancer Committee Guidelines - Update 2022-2024: management of kidney cancer.

AIM: To update the recommendations for the management of kidney cancers. METHODS: A systematic review of the literature was conducted from 2015 to 2022. The most relevant articles on the diagnosis, classification, surgical treatment, medical treatment and follow-up of kidney cancer were selected and incorporated into the recommendations. Therefore, the recommendations were updated while specifying the level of evidence (high or low). RESULTS: The gold standard for the diagnosis and evaluation of kidney cancer is contrast-enhanced chest and abdominal CT. MRI and contrast-enhanced ultrasound are indicated in special cases. Percutaneous biopsy is recommended in situations where the results will influence the therapeutic decision. Renal tumours should be classified according to the pTNM 2017 classification, the WHO 2022 classification and the ISUP nucleolar grade. Metastatic kidney cancer should be classified according to the IMDC criteria. Partial nephrectomy is the gold standard treatment for T1a tumours and can be performed by an open approach, by laparoscopy or by robot-guidance. Active surveillance of tumours less than 2cm in size can be considered regardless of the patient's age. Ablative therapies and active surveillance are options in elderly patients with comorbidity. T1b tumours should be treated by partial or radical nephrectomy depending on the complexity of the tumour. Radical nephrectomy is the first-line treatment for locally advanced cancers. Adjuvant treatment with pembrolizumab should be considered in patients at intermediate and high risk for recurrence after nephrectomy. In metastatic patients: Immediate cytoreductive nephrectomy may be offered to oligometastatic patients in combination with local treatment of metastases if this can be complete and delayed cytoreductive nephrectomy can be proposed for patients with a complete response or a significant partial response. Medical treatment should be proposed as first-line therapy for patients with a poor or intermediate prognosis. Surgical or local treatment of metastases can be proposed in case of single or oligo-metastases. The recommended first-line drugs for metastatic patients with clear cell renal carcinoma are the combinations axitinib/pembrolizumab, nivolumab/ipililumab, nivolumab/cabozantinib and lenvatinib/pembrolizumab. Cabozantinib is the recommended first-line treatment for patients with metastatic papillary carcinoma. Cystic tumours should be classified according to the Bosniak classification. Surgical removal should be proposed as a priority for Bosniak III and IV lesions. It is recommended that patient monitoring be adapted to the aggressiveness of the tumour. CONCLUSION: These updated recommendations are a reference that will allow French and French-speaking practitioners to improve kidney cancer management.

[French ccAFU guidelines - update 2020-2022: management of kidney cancer]. / Recommandations françaises du Comité de cancérologie de l'AFU ­ actualisation 2020­2022 : prise en charge du cancer du rein.

OBJECTIVE: - To update the French guidelines on kidney cancer. METHODS: - A systematic review of the literature between 2015 and 2020 was performed. The most relevant articles regarding the diagnosis, the classification, surgical treatment, medical treatment and follow-up of kidney cancer were retrieved and included in the new guidelines. The guidelines were updated with corresponding levels of evidence. RESULTS: - Thoraco-abdominal CT scan with injection is the best radiological exam for the diagnosis of kidney cancer. MRI and contrast ultra-sound can be useful in some cases. Percutaneous biopsy is recommended when histological results will affect clinical decision. Renal tumours must be classified according to pTNM 2017 classification and ISUP grade. Metastatic kidney cancers must be classified according to IMDC criteria. Partial nephrectomy is the recommended treatment for T1a tumours and can be done through an open, laparoscopic or robotic access. T1b tumours can be treated by partial or total nephrectomy according to tumour complexity. Radical nephrectomy is the recommended treatment of advanced localized tumours. There is no recommended adjuvant treatment. In metastatic patients: cyto-reductive nephrectomy can be offered in case of good prognosis; medical treatment must be counseled first in case of intermediate or bad prognosis. Surgical or local treatment of metastases should be considered in case of solitary lesion or oligo-metastases. First line recommended drugs in metastatic patients include the associations axitinib/pembrolizumab and nivolumab/ipilimumab. Cystic tumours must be classified according to Bosniak Classification. Surgical excision should be offered to patients with Bosniak III and IV lesions. It is recommended to follow patients clinically and with imaging according to tumour aggressiveness. CONCLUSION: - These updated recommendations should assist French speaking urologists for their management of kidney cancers.

Tunable High Spatio-Spectral Purity Undulator Radiation from a Transported Laser Plasma Accelerated Electron Beam.

Undulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200-300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.

Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection.

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11-13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low (<0.1% at 24 h) but reached a local concentration of ≥20 mg/L (>20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.

Long-term oncological outcomes of cystic renal cell carcinoma according to the Bosniak classification.

OBJECTIVES: To evaluate the prognostic role of the Bosniak classification on the long-term oncological outcomes of cystic renal cell carcinomas. MATERIAL AND METHOD: In a national multicentric retrospective study, we included patients treated surgically for localized cystic RCC from 2000 to 2010. Patients with a follow-up of less than 4 years, benign tumors, and ablative treatments were excluded. The primary outcome was disease-free survival. RESULTS: 152 patients met the inclusion criteria: Bosniak II (6%), III (53%), IV (41%), with a median follow-up of 61 (12-179) months. Characteristics of the population and the tumors were [median, (min-max)] age 57 (25-84) years old, tumor size 43 mm (20-280), RENAL score 7 (4-12), PADUA score 8 (5-14). Treatments were 55% partial nephrectomy, 45% radical nephrectomy, 74% open surgery, and 26% laparoscopy. In pathological report, cystic RCC were mainly of low grade (1-2, 77%) and low stage (pT1, 81%). The two main histological subtypes were conventional (56%) and papillary (23%) RCC. Staging at presentation and histological characteristics were similar between Bosniak III and IV, except for high grade which was more common in Bosniak IV (12 vs 36%, p < 0.01). The Bosniak classification was not predictive of the recurrence, as 5- and 10-year disease-free survival were similar in Bosniak III and IV (92% vs 92% and 84% vs 83%, p = 0.60). CONCLUSION: The Bosniak classification is predictive of the risk of malignancy but not of the oncological prognosis. Regardless of the initial Bosniak categories, almost all cystic RCCs were of low stage/grade and had low long-term recurrence rate.

Recurrence of Goodpasture syndrome without circulating anti-glomerular basement membrane antibodies after kidney transplant, a case report.

BACKGROUND: Goodpasture Syndrome (GS) is an autoimmune disease caused by the development of auto-antibodies against the Glomerular Basement Membrane (GBM). Linear deposit of immunoglobulins G on the GBM detected by immunofluorescence analysis of renal biopsies is a GS pathognomonic finding. GS is commonly monophasic and its incidence is 1.6 case per million per year. CASE PRESENTATION: This report describes and discusses the case of a 40-year-old woman who one year after allograft kidney transplant, presented with acute pulmonary and renal symptoms of GS, leading to acute graft dysfunction, without circulating anti-GBM antibody detection in laboratory assays. She received a living donor kidney transplant 4 years after the first diagnosis of GS without circulating anti-GBM antibodies, when considered in remission. CONCLUSIONS: In both episodes, the diagnosis of GS was based exclusively on the kidney biopsy that showed rapidly progressing glomerulonephritis with deposition of immunoglobulins G on the GBM. Although rare, the management of patients with GS without circulating anti-GBM antibodies is difficult due to the lack of standardized follow-up guidelines to reduce the risk of GS recurrence after kidney transplantation.

RETRACTED: Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : prise en charge du cancer du reinFrench ccAFU guidelines ­ Update 2018­2020: Management of kidney cancer / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : prise en charge du cancer du rein.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: DOI:10.1016/j.purol.2019.01.004. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the DOI:10.1016/j.purol.2019.01.004. That newer version of the text should be used when citing the article.

[French ccAFU guidelines - Update 2018-2020: Management of kidney cancer]. / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : prise en charge du cancer du rein.

OBJECTIVE: To update the French guidelines on kidney cancer. METHODS: A systematic review of the literature between 2015 and 2018 was performed. The most relevant articles regarding the diagnosis, the classification, surgical treatment, medical treatment and follow-up of kidney cancer were retrieved and included in the new guidelines. The guidelines were updated with corresponding levels of evidence. RESULTS: Thoraco-abdominal CT scan with injection is the best radiological exam for the diagnosis of kidney cancer. MRI and contrast ultrasound can be useful in some cases. Percutaneous biopsy is recommended when histological results will affect clinical decision. Renal tumours must be classified according to pTNM 2017 classification and ISUP grade. Metastatic kidney cancers must be classified according to IMDC criteria. Partial nephrectomy is the recommended treatment for T1a tumours and can be done through an open, laparoscopic or robotic access. T1b tumours can be treated by partial or total nephrectomy according to tumour complexity. Radical nephrectomy is the recommended treatment of advanced localized tumours. In metastatic patients: cytoreductive nephrectomy is recommended in case of good prognosis; medical treatment must be offered first in case of intermediate or bad prognosis. Surgical or local treatment of metastases should be considered in case of solitary lesion or oligo-metastases. First-line recommended drugs in metastatic patients include sunitinib, pazopanib, and the association nivolumab/ipilimumab. Cabozantinib can be offered in option in intermediate and bad prognostic patients. Cystic tumours must be classified according to Bosniak Classification. Surgical excision should be offered to patients with Bosniak III and IV lesions. It is recommended to follow patients clinically and with imaging according to tumour aggressiveness. CONCLUSION: These updated recommendations should assist French speaking urologists for their management of kidney cancers.

[Tubulocystic renal cell carcinoma with poorly differentiated foci]. / Carcinome rénal tubulokystique avec composante peu différenciée.

Tubulocystic renal cell carcinoma is a rare tumor with an indolent behavior in the majority of cases. In contrast, tubulocystic renal cell carcinoma with poorly differentiated foci has a bad prognosis with an aggressive and metastatic behavior. We present the case of a patient diagnosed with tubulocystic renal cell carcinoma with poorly differentiated foci.

Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract.

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

[CCAFU french national guidelines 2016-2018 on renal cancer]. / Recommandations en onco-urologie 2016-2018 du CCAFU : Cancer du rein.

The previous guidelines from the Cancer Committee of the Association Française d'Urologie were published in 2013. We wanted this new version to be simple, clear and straightforward. All significant recent publications on kidney cancer have been included. The main changes compared to 2013 are the following: © 2016 Elsevier Masson SAS. All rights reserved.

[Oncologic and perioperative outcomes of robot-assisted radical cystectomy: A single-center prospective series]. / Résultats oncologiques et périopératoires de la cystectomie totale robot-assistée pour cancer : une série prospective monocentrique.

INTRODUCTION: The aim of this study was to report perioperative and oncological outcomes of robot-assisted radical cystectomy (RARC) in a single-center series and to evaluate the impact of the experience on perioperative outcomes. METHODS: Between March 2012 and January 2016, 41 patients underwent RARC associated with extended pelvic lymphadenectomy for muscle-invasive bladder cancer. All RARC included were performed by a single-surgeon in one center. Perioperative and oncological datas were collected prospectively. Recurrence-free (RFS), overall (OS) and cancer-specific survivals (CSS) were estimated using the Kaplan-Meier Method. The impact of the experience on perioperative data was estimated using Spearman's correlation test. RESULTS: Mean age was 67,7years (±10.6). Most patients underwent neoadjuvant chemotherapy (73.2%). Mean operative time and mean estimated blood loss were respectively 319.5minutes (±85.3) and 662.5mL (±360.9). Eight patients needed perioperative blood transfusion (19.5%). Conversion to open surgery was necessary in 3 cases (7.3%). Ileal neobladder was performed in 26.8% of the cases (54.5% being performed intracorporeal), and non-continent urinary diversion in 73.2%. Mean nodal yield was 17.7 (±9.3). Positive surgical margins were observed in 1 patient (2.3%). Mean length of stay was 13.2 days (±9.8). Postoperative complication rate was 46,3%. After a median follow-up of 16months, estimated 2 year-OS and CSS were respectively 62 and 76.1%. Estimated 2-year RFS was 67.6%. Perioperative outcomes improved with experience with a significant decrease in operative time (P=0.04) and a significant increase of nodal yield (P=0.05). CONCLUSION: In this single-center prospective study, satisfactory perioperative and oncological outcomes after RARC were observed despite the learning curve. Perioperative outcomes improved with surgeon's experience. Further studies are needed to confirm these findings. LEVEL OF EVIDENCE: 4.

[Pathological advances in renal, prostatic, bladder and testis neoplasia]. / Actualités en pathologie tumorale rénale, prostatique, vésicale et testiculaire.

INTRODUCTION: The ISUP (International Society of Urological Pathology) Consensus Conferences between 2012 and 2015 made recommendations regarding the classification, staging, prognostic factors of adult tumors from kidney, prostate, bladder and testis. The main points of these recommendations are highlighted in this article. MATERIALS AND METHODS: This article is based on a systematic literature search by using different keywords "cancer, kidney, prostate, bladder, testis, pathology, classification" from Pubmed database. Only publications between 2012 and 2015 were retained. RESULTS: The different Consensus conferences since 2012 in uropathology have provided international guidelines for the classification, grading and staging of tumors in kidney, bladder, prostate and testis. We identified in this article the main points of these new guidelines that are about to be published in the new 2016 WHO classification of urogenital tract tumors in adult. CONCLUSION: New pathological guidelines in urogenital tumors have to be taken into account for a better diagnosis and therapy.

[Difficulties and limitations in conducting translational research in thoracic oncology. A practical example]. / Difficultés et limites dans la conduite d'une étude translationnelle en oncologie thoracique. Un exemple pratique.

INTRODUCTION: In a first study, we identified signatures of 3 mRNAs (semaphorin 3D [SEMA3D], cytokeratin 16 [KRT16] and UL16 binding protein 2 [ULBP2]) associated to response to a cisplatin-vinorelbin chemotherapy and to survival of advanced non-small cell lung cancers (NSCLC). MATERIAL AND METHODS: The aim of this study was to develop immunohistochemistry tests for KRT16, ULBP2 and SEMA3D and to test proteins expression for prediction of response and survival in biopsies of the same patients. RESULTS: We were not able to reproduce by the protein expression study the signature predicting response to chemotherapy in advanced NSCLC. CONCLUSION: We highlight the difficulties of translational research in thoracic oncology emphasizing the complexity in obtaining adequate tissue samples and the difficulties in conduction and transposing in routine practice high throughput technique for transcriptomic analyses.

[Impact of robotic assistance on the use and the outcomes of nephron-sparing surgery: A single center experience]. / Impact de l'assistance robotique sur la pratique et les résultats de la chirurgie rénale conservatrice : une expérience monocentrique.

INTRODUCTION: The aim of this study was to assess the impact of the acquisition of a Da Vinci® robot on the use and outcomes of partial nephrectomy (PN). PATIENTS AND METHODS: It was a single center retrospective study including 280 patients who underwent PN from January 2006 to May 2013. The number of PN, tumors and patients' characteristics and perioperative outcomes have been assessed over 3 periods defined according to the main surgical approach: 2006-2008 (open PN), 2008-2010 (laparoscopic PN) and 2010-2013 (robotic PN). RESULTS: Over the study period, the surgical approach has changed significantly in favor of minimally-invasive surgery and especially robotic approach. The PN/nephrectomy rate has also evolved to a higher proportion of PN over radical nephrectomy (P=0.002). No significant difference was noted between the three periods in terms of tumor size but there was a higher rate of highly complex tumors (RENAL score≥10) during the last period (10.7%; 18.6% and 33.2%; P=0.04). Warm ischemia time increased from 2006-2008 to 2008-2010 (26 vs. 23minutes) but decreased thereafter during the robotic era (14.5minutes; P<0.001). Regarding postoperative outcomes, the only change was a decreased length of stay over time (P=0.003). CONCLUSION: In this single center series, the robotic approach was associated with a spread of PN and with an improvement of nephron-sparing surgery outcomes. LEVEL OF EVIDENCE: 4.

[Implementation of an oncological care program in a multidisciplinary clinic]. / Implémentation d'un programme de soins oncologiques en consultation multidisciplinaire.

INTRODUCTION: A working group has highlighted guidelines in thoracic oncology in Europe without study of their implementation, due to a lack of data. METHODS: The records of 354 untreated lung cancer patients seen between January 2009 and December 2012 were reviewed. Any new treatment should have been proposed by a multidisciplinary consultation (MDC) in accordance with an oncology care program (OCP) based on the European Lung Cancer Working Party guidelines. RESULTS: For the 354 patients, there were 636 MDC (332, 176, 81 and 47 in 1st, 2nd, 3rd and subsequent lines). For the first line, the MDC rate was 88%, in accordance with the OCP, and 75% of treatments were in agreement with the guidelines. For the 2nd and 3rd lines, the rates were 93% and 92% respectively (MDC), 90 and 89% (OCP), 55 and 63% (guidelines). In the first line, the main causes of non-compliance with the OCP were patient's refusal or doctor's choice and with guidelines a lack of adequate recommendations for specific situations such as comorbidities or the appearance of new treatments. CONCLUSION: The vast majority of patients are the subject of a MDC with a high rate of application of OCP. Guidelines should be updated regularly to incorporate new treatments.