Actualités néphrologiques. Arnaud Méjean

Transcription

1 Actualités néphrologiques Arnaud Méjean

2 Disclosures Pfizer, Novartis, GSK, BMS, Roche, Ipsen, Pierre Fabre, Astellas, Janssen, Ferring

3 Epidemiology 7 th rank of cancer Incidence 2012 : news cases (67% men) 3957 deaths 2% / an male % / an female

4 Diagnosis and evaluation? US and CEUS CT-Scan (3 times +1) RMI (cysts, SRM, CKD) Veinous extension egfr Biopsy : only if it changes the strategy Spe et sens > 99% Histological type : 90 à 96 % Grade : 43 à 93 %

5 National Cancer Institute. SEER 2008, cancer of the kidney

6 Repartition by stage from a large french multicentric database UroCCR (4771 patients 25 expert centers) Acknowledgement JC Bernhardt Metast atic [POUR CEN Locoregional [POURCE NTAGE] ctnm Localized [POURCE NTAGE]

7 TNM Nucleoraly Grade ISUP replaces nuclear grade of Fuhrman

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9 Traitement of localized disease T < 4 cm = PN 4 < T < 7 cm = PN > RN T > 7 cm = RN > PN² Carcinological rationnel? Fonctional rationnel?

10 RN associated at survival vs PN 648 pts, , T unique < 4 cm 358 PN, 290 RN FU : 7.1 yrs No SSD on the total population Pts < 65 yrs, OS 10 ans : 93% PN vs 82% RN (p<0.02) Thompson RH, J Urol, 2008

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12 Biaises : pts (effectif 1300 not reached) Very few specific events (12 DC / 117) 4. SSD (p=0.03) only on the intention to treat population and only in superiority test but not in noninferiority test 5. No SSD in the RCC-population!!!!!!!!!

13 adultes FU = 2.84 ans

14 Is RN a risk factor of CKD? 662 pts, , single T < 4 cm, normal controlateral kidney, normale creat 390 PN, 272 RN 26 % MDRD préop < 60 ml/ Huang WC, Lancet, 2006

15 26% pts (créat nle) sont IR avant chir A 3 ans 80% après NP 35% après NE 95% après NP 64% après NE

16 Tumeur 4 7 cm or central location Complications rates Morbidité T op, TIC, séjour Lebed and al, Urology 2010, Van Poppel and al, Eur Urol 2007, Patard and al Eur Urol 2007

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18 Push the boundaries Imperative Relative Elective Patient age, BMI, comorbidity (anticoag) Rein Tumeur CKD-EPI, perirenal fat size, location, urinary tract, peritumoral zone Perfect imagery

19 Surgical approaches Lombotomy (open) Laparoscopy Assisted Robotic Objectif : NSS ++++

20 Robotic

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22 «Intuitive Surgery» Importante evolution but robotic surgery has never created a new intervention

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24 Less radical Less invasiveness Open RN / PN Lap RN / PN Robotic PN Percutaneous Ablation Transcutaneous Ablation

25 Thérapies Mini-Invasive?? Resection Ablation

26 Radiofrequency ablation (RFA) Electromagnetic ondes (500 khz) Friction moléculaire T up to C Coagulation and necrose Material : sonde, generator, computer Limites : evaluation (MRI, CT, Biopsie??) and enhancement < 10 UH

27 General principle +

28 Best success factors Size < 3,5 cm Non central location Zagoria, Breen, 2007 Gervais 2005

29 Cryoablation (CA) Spring : argon ou liquid nitrogen Dead T : - 40 C 3 phases cycle : freezing heat frezzing Evaluation «ice ball» (MRI, CT)

30 CA : important equipment

31 Indications SMRs Patients > 70 ans VHL : 1st procedure or recurrence? CKD Co-morbidity Local recurrence after PN

32 Locally advanced cancer Surgery +++ NO neoadjuvant treatment excepted case/case Abel and al, Eur Urol, 2011

33 Male, 65, haematuria, left renal tumor, No mets

34 Male 50, pulmonary embolism, No mets

35 Adjuvant trials RCC Essai Molécules Dureé ttt Assure Sunitinib vs sorafenib vs placebo Histo PE Nb pts 1 RCC DFS 1943 S-Trac Sunitinib vs placebo 1 ccrcc DFS 615 Ariser Girentuximab vs placebo 0.5 ccrcc DFS + OS Protect Pazobanib vs placebo 1 ccrcc DFS Everest Everolimus vs placebo 1 RCC DFS 1545 Sorce Sorafenib(1vs3) vs placebo 1 RCC DFS 1556 Atlas Axitinib vs placebo 3 ccrcc DFS 703 Immotion 010 Prosper Atezolizumab vs placebo 1 Sarcomatoïd DFS 684 En cours Nivolumab (adj/neoadj) vs chirurgie 0.5 RCC RFS 766 En cours

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37 mrcc : Cytoreductive Nephrectomy (CN) or not CN? For who?

38 Flanigan et al SWOG, 2001 Mickisch et al EORTC, 2001 Nx + IFN vs IFN 13.6 mois vs 7.8 But ECOG 0-1

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40 Targeted therapies Mejean A et Lebret T, Prog Urol, 2010

41 CARMENA design mrcc with clear-cell component Randomisation 1:1 Arm A Nephrectomy + Sunitinib 50 mg 4/2 Arm B Stratification factors: MSKCC score Country Sunitinib 50 mg 4/2

42 Included patients ARMENA I Global inclusions Date : 2017/04/20 Global inclusions : 438/576 CARMENA- Inclusion Curve August January June November April September February July December May October March August 2014 Months Achieved inclusions 01 January June November April 2016 Target inclusions 01 September February July 2017

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45 Protocoles Neo-adj, Adjuvant Monotherapy Combination.. Mais quel est le futur?

46 Définir des séquences de traitement

47 Marco Gerlinger et al

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50 Characteristics of the four molecular subgroups of ccrcc B Beuselink et al, Clin Cancer Res, 21, , 2015

51 Abundant lymphocytes Lack of TLS Abundant immature DC Abundant M2 Macrophages Highly vascularized Abundant Fibroblasts IL-1, IL-6 and TNF-a TGF-B and VEGF PD-L1 and PD-L2 expression THE IMMUNE WHEEL TLS Abundant lymphocytes Abundant TLS and associated mature DC Abundant CTL Abundant M1 Macrophages Abundant Antibodies and B cells Intermediate vascularization Intermediate Fibroblasts IFN-y and CXCL13 Inflammatory Immunogenic By Courtesy of HW Fridman Immature DC Mature DC T cell M1 Mφ M2 Mφ Escaping Low lymphocyte density Lack of TLS, DC and CTL Low levels of cytokines Intermediate vascularization Intermediate Fibroblasts

52 Conclusion Dogme of RN is dead Developpement pf PN ++ Robotic surger Mini-invasive ablative therapies ++ Targeted therapies Check points inhibitors ++ But the big bang has to come.