Locally Advanced Kidney Cancer Cavotomy, Pancreatic Resection our current Experience and Results

Locally Advanced Kidney Cancer Cavotomy, Pancreatic Resection our current Experience and Results Dr. Kolombo Ivan, MD, FEBU Klézl P, Hruška M -1, Dvořáček M, Gürlich R, Štefka J, Havlůj L -2, Kindlová E, Dvořák J, Loukotková L -3, Eis V -4, Grill R 1* 1 - Department of Urology, 2 Department of Surgery, 3 - Department Radiotherapy and Oncology, 4 - Department of Pathology - University Hospital Vinohrady Prague, Czech Republic, * Corresponding author Cluj 2015 Dr. Ivan Kolombo, FEBU 1 Cavotomy & Trombectomy & Pancreatic Resection for RCC

Epidemiology & Kidney Cancer The incidence of RCC in the Czech Republic is highest in the world Dušek L, Mužík J, Kubásek M a kol. Epidemiologie zhoubných nádorů v České republice [online]. http://www.svod.cz. ÚZIS ČR (Institute of health information and statistics of the Czech republic - IHIS CR) http://www.uzis.cz Znojmo 2014 Cavotomy & Trombectomy & Pancreatic Resection for RCC Dr. Ivan Kolombo, FEBU

Epidemiology & Kidney Cancer The mortality of RCC in the Czech Republic is highest in the world Dušek L, Mužík J, Kubásek M a kol. Epidemiologie zhoubných nádorů v České republice [online]. http://www.svod.cz. ÚZIS ČR (Institute of health information and statistics of the Czech republic - IHIS CR) http://www.uzis.cz Znojmo 2014 Dr. Ivan Kolombo, FEBU

Epidemiology & Kidney Cancer Incidence has been rising by about 2% per year in many developed countries. Dušek L, Mužík J, Kubásek M a kol. Epidemiologie zhoubných nádorů v České republice [online]. http://www.svod.cz. ÚZIS ČR (Institute of health information and statistics of the Czech republic - IHIS CR) http://www.uzis.cz Znojmo 2014 Dr. Ivan Kolombo, FEBU

Epidemiology & Kidney Cancer Locally advenced RCC stage III-IV (25%). Dušek L, Mužík J, Kubásek M a kol. Epidemiologie zhoubných nádorů v České republice [online]. http://www.svod.cz. ÚZIS ČR (Institute of health information and statistics of the Czech republic - IHIS CR) http://www.uzis.cz Znojmo 2014 Dr. Ivan Kolombo, FEBU

Cavotomy & Tumor Thrombectomy for Kidney Cancer Renal cell carcinoma (RCC) is the most malignant urological tumour. The incidence of RCC in the Czech Republic is currently highest in the world. The incidence has been rising by about 2% per year in many developed countries. Approximately 30% of RCC patients (pts) will have metastatic disease at the time of presentation. ICS 2015 Cavotomy & Trombectomy & Pancreatic Resection for RCC Dr. Ivan Kolombo, FEBU 6

Cavotomy & Tumor Thrombectomy for Kidney Cancer The most common sites for metastasis of RCC are lung (50%), bones (33%), liver (8%), cutaneous (11%) and brain (3%) etc. One of the unique features of RCC is its frequent pattern of growth intraluminally into the renal venous circulation, also known as venous tumor thrombus. In extreme cases this growth may extend into inferior vena cava (IVC) with cephalad migration as far as the right atrium or beyond. Tumor thrombus extension to the renal vein has been reported in 30-40 % of pts, extension into the IVC in 4-10% of pts while the tumor may extend up to the right cardiac chambers in 0.5% of cases. ICS 2015 Cavotomy & Trombectomy & Pancreatic Resection for RCC Dr. Ivan Kolombo, FEBU 7

Cavotomy & Tumor Thrombectomy for Kidney Cancer ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 8

Cavotomy & Tumor Thrombectomy for Kidney Cancer ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 9

Cytoreductive nephrectomy (CNE) in the time of imunotherapy CNE improved results of systemic therapy (SWOG 8949 + EORTC 30 947) Imunotherapy of mrcc with IFN α 2b Negative imunosupresiv efect of primary tumour EORTC 30 947 improve (OS - 17 vs 7 mths (p<0.05)) RR - response rate only 6% without CNE Flanigan RC, Salmon SE, Blumenstein BA et al: Nephrectomy followed by interferon α-2b compared with interferon α-2b alone for metastatic renal cell cancer. N Engl J Med 2001; 345: 1655-9 Mickisch GH, et al: Radical nephrectomy plus interferon α-based immunotherapy compared with interferon α alone for metastatic renal cell carcinoma: a randomized trial. Lancet 2001; 358: 966-70 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Cytoreductive nephrectomy(cne) & biological targeted therapy First-Line Sunitinib vs IFN-α: PFS and Response Rate (RR) 750 pts. (Motzer RJ 2007) (RR ) 31% (sunitinib) versus 6% (IFN-α) (PFS) sunitinib více než dvakrát delší (11měsíců versus 5měsíců, p<0,000001) Sunitinib (SUN) 375 pts. SUN+CNE - 339 (90%) PFS 11 měsíců SUN - 36 (10%) PFS 6 měsíců (p = 0.0889) Combined analysis 2 studies- II. fáze hodnotící OS u 163 (97%) pts. - sunitinib (Rosenberg JE 2007) SUN+CNE - 163 (97%) - OS 20 měsíců SUN - 5 (3%) - OS 10 měsíců (p = 0.3638) Motzer RJ, et al: Sunitinib versus interferon alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mrcc): updated results and analysis of prognostic factors. J Clin Oncol, suppl 2007; 25: abstract 5024 Rosenberg JE, Motzer RJ, Michaelson MD et al: Sunitinib therapy for patients (pts) with metastatic renal cell carcinoma (mrcc): updated results of two phase II trials and prognostic factor analysis for survival. J Clin Oncol suppl 2007; 25: abstract 5095 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Cavotomy & Tumor Thrombectomy for Kidney Cancer Cytoreductive nephrectomy (CNE), followed by systemic targeted biological therapy is standard approach in the treatment of metastatic renal cell carcinoma (mrcc). CNE is also indicated for the control of severe symptoms such as haemorrhage, pain or paraneoplastic syndromes. Also in cases of established tumor thrombus extending into the inferior vena cava (IVC) is not yet available to other effective therapies. CNE solves accompanying hematuria and is followed by systemic targeted biological therapy as standard approach in the treatment of mrcc (1) 1. Ljungberg B, Bensalah K, Bex A, et al: Guidelines on Renal cell carcinoma, European Association of Urology, Eur Urol, 2015 Update March, 24 28, www.uroweb.org ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 12

Cavotomy & Tumor Thrombectomy for Kidney Cancer Untreated tumour thrombus formation in the IVC in RCC pts is a significant adverse prognostic factor. In individual cases of mrcc and satisfactory overall status is also indicated CNE + cavotomy with tumor thrombus extraction from IVC to solves accompanying hematuria. Study evaluates our current experience and results. ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 13

Cavotomy & Tumor Thrombectomy for Kidney Cancer Materials and methods: In the period (I/2014-II/2015), we performed 14 CNE for mrcc (lung, lymph nodes, adrenal glands, liver, or in the skeleton). In 4 cases on the preoperative CT scan we detected a tumor thrombus extending into the VCI. In all cases tumor trombus extend no further than the subhepatic VCI. Tumor thrombus in VCI spread from the affected renal vein cranialy at a distance of 5.5 cm (4-7 cm). ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 14

Cavotomy & Tumor Thrombectomy for Kidney Cancer Materials and methods: Two men and two women, when the average age was 59 years (47-69years). In 3 cases carcinoma arising from the right kidney and 1 from left kidney. Clinical staging was ct3b, N0-1, M1. Surgery was done, with cooperation of vascular surgeon (cavotomy and thrombus extraction from VCI with CNE). Abdominal approach was sufficient to loading tourniquets or vascular clamps on the VCI in the subdiaphragmatic course. Ligation of the short hepatic veins was needed in 1 case. ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 15

Cavotomy & Tumor Thrombectomy for Kidney Cancer Fig 1+2: Befor right CNE with IVC thrombectomy ligation of right renal artery in interaortocaval space is performed and venous clamps (or wessel tourniquet) are placed above the suprarenal and infrarenal vena cava thrombus levels and on opposite renal vein. After this preparation the cavotomy and tumor thrombectomy is safety performed (Fig 1). Completely enblock removed the right kidney with tumor and with the surrounding tissues (Fig 2). ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 16

Cavotomy & Tumor Thrombectomy for Kidney Cancer Results: Subcostal approach was used, extended as necessary to the contralateral side. The main goal of surgery is complete thrombus removal without tumor fragmentation so we used long venotomy on fully exposed involved IVC is recommended for successful result. Thrombus in IVC was carefully assessed and venous clamps placed above the suprarenal and infrarenal vena cava thrombus levels. The opposite renal vein is gently secured, cavotomy incision made, and part of tumour thrombus removed. Our surgical technique we have previously described in detail (2). 2. Kolombo I, Klézl P, et al: Kidney cancer from the perspective of urologist. Onkologie 2014; 8(5): 201-207 ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 17

Cavotomy & Tumor Thrombectomy for Kidney Cancer Results: Mean operative time was 200min (150-250). Blood loss of 3000 ml (2000-3700 ml), which was continuously substitute transfuse of blood and frozen plasma (ratio of 2: 1). Surgery was without complications. In two cases the conservative treatment was necessary for paralytic ileus. Surgical revision was not needed and the average length of hospital stay was 12 days (7-17 days). Histology reveal clear RCC. All pts after surgery were indicated for targeted therapy. ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 18

Cavotomy & Tumor Thrombectomy for Kidney Cancer Discussion: mrcc pts with untreated metastatic disease have a 5year survival of 0-18%. CNE significantly prolonged survival and is standard part of a multimodal approach for selected groups of pts with mrcc in the era of imunotherapy and also in current era of targeted biological treatment. Radical nephrectomy with IVC thrombectomy remains the most effective therapeutic option in pts with RCC and IVC tumor thrombus. The surgical treatment of RCC with a tumor trombus extending to IVC is dependent on the disease site, thrombus extension level and the degree of IVC patency. CNE and IVC thrombectomy can be safely performed in selected pts with metastatic disease and should be considered as an integral part of the treatment approach for pts with mrcc (3). Furthermore, in pts receiving biologic therapy, CNE with IVC thrombectomy may enable a better quality of life and prolonged survival. 3. Slaton JW1, Balbay MD, Levy DA, et at: Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma. Urology 1997 50(5):673-7. ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 19

Cavotomy & Tumor Thrombectomy for Kidney Cancer Conclusions: According experience of our interdisciplinary team the complex surgery as CNE and IVC thrombectomy can be performed in selected pts with acceptable complication rates and should be considered as an integral part of the multimodal treatment approach with subsequent targeted therapy for pts with mrcc and IVC tumor thrombi. CNE in pts with thrombus and mrcc is not associated with an increase in the extent of surgery, morbidity or mortality compared with their counterparts with nonmetastatic disease (5). 5. Zisman A, Pantuck AJ, Chao DH, et al: Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for advanced disease associated with an increased complication rate? J Urol. 2002; 168: 962-7 ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 20

Cavotomy & Tumor Thrombectomy for Kidney Cancer Conclusions: CNE and IVC thrombectomy can be performed with acceptable complication rates and should be considered as an integral part of the treatment approach for pts with mrcc also for a more extensive IVC tumor thrombi than we found in our cases also with level III and IV (4). Surgery for more cephalic extension of the thrombus is more demanding and closely related to perioperative morbidity. 4. Westesson KE, Klink JC, Rabets JC, et al: Surgical outcomes after cytoreductive nephrectomy with inferior vena cava thrombectomy.urology. 2014; 84(6):1414-9 ICS 2015 Cavotomy & Tumor Trombectomy for RCC Dr. Ivan Kolombo, FEBU 21

CNE & symptomatic RCC: symptomatic RCC Clinical trias Hematuria (až v 60%) Back pain (45%) Palpable tumour (35%) Paraneoplastick symptoms : "nádor internistů (30%) (hypertenzion a polycytémie, anemie, hyperkalcémie, amyloidosis nebo hepatopatie Staufferův syndrom ) Cluj 2015 Ivan & Jitka Kolombovi

Adapt study for mrcc Cluj 2015 Cavotomy & Trombectomy & Pancreatic Resection for RCC Dr. Ivan Kolombo, FEBU

TMC Texas Medical Center USA Left upper abdominal quadrantectomy Znojmo 2014 Ivan & Jitka Kolombovi

Vena cava inferior s nádorovým trombem RCC 5 a 10letý DSS (disease specific survival rate) - 36% a 24% při průběhu sledování se vzdálené metastázy objeví u více než 62% nemocných Klatte T, Pantuck AJ, Riggs SB, Kleid MD, Shuch B, Zomorodian N, Kabbinavar FF, Belldegrun AS: Prognostic factors for renal cell carcinoma with tumor thrombus extension. J Urol 2007 Oct;178(4 Pt 1):1189-95 Znojmo 2014 Ivan & Jitka Kolombovi

Thank you for your attention ICS 2015 Salvage Surgery & Fast Track Dr. Ivan Kolombo, FEBU 28

Modern Radical Cystectomy Radical Cystectomy Removal of bladder with surrounding fat Prostate/seminal vesicles (males) Uterus/fallopian tubes/ovaries/cervix (females) + Urethrectomy Pelvic Lymphadenectomy More is better Urinary Diversion Ileal conduit Continent cutaneous reservoir Orthotopic neobladder Znojmo 2014 Bladder Cancer & Cystectomy Dr. Ivan Kolombo, FEBU 29

Radical Cystectomy - OUTCOMES Stein JP, et al. J Clin Oncol 19:666, 2001 Znojmo 2014 Bladder Cancer & Cystectomy Dr. Ivan Kolombo, FEBU 30

Examples of Orthotopic Neobladders Figure 82-4 Construction of the ileal neobladder (Studer pouch) with an isoperistaltic afferent ileal limb. A, A 60- to 65-cm distal ileal segment is isolated (approximately 25 cm proximal to the ileocecal valve) and folded into a U configuration. Note that the distal 40 cm of ileum constitutes the U shape and is opened on the antimesenteric border; the more proximal 20 to 25 cm of ileum remains intact (afferent limb). B, The posterior plate of the reservoir is formed by joining the medial borders of the limbs with a continuous running suture. The ureteroileal anastomoses are performed in a standard endto-side technique to the proximal portion (afferent limb) of the ileum. Ureteral stents are used and brought out anteriorly through separate stab wounds. C, The reservoir is folded and oversewn (anterior wall). D, Before complete closure, a buttonhole opening is made in the most dependent (caudal) portion of the reservoir. E, The urethroenteric anastomosis is performed. F, A cystostomy tube is placed, and the reservoir is closed completely.

Examples of Orthotopic Neobladders Figure 82-3 Construction of the Hautmann ileal neobladder. A, A 70-cm portion of terminal ileum is selected. Note that the isolated segment of ileum is incised on the antimesenteric border. B, The ileum is arranged into an M or W configuration with the four limbs sutured to one another. C, After a buttonhole of ileum is removed on an antimesenteric portion of the ileum, the urethroenteric anastomosis is performed. The ureteral implants (Le Duc) are performed and stented, and the reservoir is then closed in a side-to-side manner.

Small-calibre Catheter Conduit The Yang - Monti procedure and the Chapple modification Znojmo 2014 Dr. Ivan Kolombo, FEBU 33

Karcinom ledviny nejletálnější urologický karcinom RCC může metastazovat do mízních uzlin a prakticky do jakéhokoliv orgánu. Nejčastějším místem metastatického postižení jsou plíce. Skelet, mozek, nadledviny a játra patří mezi další relativně častá místa možných metastáz. V literatuře jsou však hlášeny další méně obvyklé lokalizace metastáz při RCC jako je pankreas, štítná žláza, vedlejší nosní dutiny, močový měchýř a řada dalších. Odstraňování vzdálených solitárních metastáz je dlouhodobě považováno za optimální postup pokud je výkon technicky možný. V řadě studií je v tomto případě dosahováno 5letého přežití kolem 35%. Ještě lepších výsledků je dosahováno pokud se jednalo o resekci solitární plicní metastázy a je hlášeno 5leté přežití 54% (47). Příznivé výsledky je možné dosáhnout i při dalších resekcích v rámci druhé či třetí rekurence metastáz. Znojmo 2014 Ivan & Jitka Kolombovi

Resekce metastáz RCC Resekce metastáz je dlouhodobě považováno za optimální postup pokud je výkon technicky možný. V řadě studií je v tomto případě dosahováno 5letého přežití kolem 35%. Nejlepších výsledků resekci solitární plicní metastázy a je hlášeno 5leté přežití 54% (47). Kavolius JP, Mastorakos DP, Pavlovich C et al: Resection of metastatic renal cell carcinoma. J Clin Oncol 1998; 16: 2261-6 Znojmo 2014 Uroonkologie & robotické systémy Ivan & Jitka Kolombovi

Resekce lymfatických uzlin RCC TxN+M0 Výsledky M.D. Anderson Cancer Center (Houston, TX USA) 40 nemocných s RCC- primárně TxN+M0 -chirurgická léčba retroperitoneální lymfadenektomii - pn1(30%), pn2 (70%) OS- pn1-35.7 měsíce signifikantně lepší (p<0,029) pn2-14.5 měsíce Canfield SE, Kamat AM, Sanchez-Ortiz RF et al: Renal cell carcinoma with nodal metastases in the abscence of distant metastatic disease (clinical stage TxN1-2M0): the impact of aggressive surgical resection on patient outcome. J Urol 2006; 175: 864-9 Znojmo 2014 Ivan & Jitka Kolombovi

Resekce lymfatických uzlin RCC TxN+M0 Rutinní retroperitoneální lymfadenektomie bez zjevné patolog Histologická pozitivita pouze v 3,3% (Blom JH, 1999) Retroperitoneální lymfadenektomie TxN1-2M0 Benefit při agresivně provedené lymfadenektomii (Canfield SE, 2006) Blom JH,, et al: Radical nephrectomy with and without lymph node dissection: preliminary results of the EORTC randomized phase III protocol 30881. EORTC Genitourina Group. Eur Urol 1999; 36: 570-5 Canfield SE, Kamat AM, Sanchez-Ortiz RF et al: Renal cell carcinoma with nodal metastases in the abscence of distant metastatic disease (clinical stage TxN1-2M0): the impact of aggressive surgical resection on patient outcome. J Urol 2006; 175: 864-9 Znojmo 2014 Ivan & Jitka Kolombovi

Resekce kostních metastáz RCC osteolytické velmi destruktivní extrémně hypervaskularizované vysoké riziko kostních komplikací SREs selektivní embolizace před somatektomií Kolombo I, Kolombová J, Dvořáček J, Hanuš T, et al.: Skeletální postižení v uroonkologii, Galén 2005 Kolombo I, Chrobok J, Poněšický J et al: Our first experience with replacement for vertebral body by Synex device for spine metastatic disease of urooncological patients. Eur Urol Meetings 2007; Vol 2, Issue 7, Abstract 98 Znojmo 2014 Ivan & Jitka Kolombovi

Resekce kostních metastáz RCC celá škála chirurgicko-ortopedických výkonů 368 skeletálních matastáz léčených chirurgicky výsledné přežívání -solitární a vícečetné meta OS po 1, 2 a 5letech bylo 47%, 30% a 11% Lin PP, Mirza AN, Lewis VO et al: Patient survival after surgery for osseous metastases from renal cell carcinoma. J Bone Joint Surg Am 2007; 89: 1794-801 Znojmo 2014 Ivan & Jitka Kolombovi

Vertebroplastkiky & cementoplastiky Znojmo 2014 Ivan & Jitka Kolombovi

Komplexní th. kostních metastáz RCC zoledronát signifikantně oddaluje vznik skeletálních komplikací o téměř jeden rok (352 dnů resp.) snížení rizika rozvoje kostních komplikací u RCC dokonce o 58% zoledronát signifikantně prodlužuje dobu do progrese onemocnění u RCC Lipton A, et al: Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 2003 Sep 1; 98(5): 962-969 Znojmo 2014 Ivan & Jitka Kolombovi

Komplexní th. kostních metastáz RCC indikace k operační léčbě kostních metastáz hrozící či vzniklé kostní komplikace patologické zlomeniny, progredující kompresivní neuropatie, radikulopatie či myelopatie zoledronát signifikantně snižuje riziko SREs u RCC Kolombo I, Kolombová J, Dvořáček J, Hanuš T, et al.: Skeletální postižení v uroonkologii, Galén 2005 Lipton A, et al: Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 2003 Sep 1; 98(5): 962-969 Znojmo 2014 Ivan & Jitka Kolombovi

Komplexní th. kostních metastáz RCC konvenční otevřené ortopedické výkony náročné méně invazivní alternativní postupy perkutánní radiofrekvenční ablace metastáz vyplnění kavity cementoplastika, vertebroplastika Schaefe O, et al: Technical innovation. Combined treatment of a spinal metastasis with radiofrequency heat ablation and vertebroplasty. AJR Am J Roentgenol 2003 Apr;180(4):1075-7 Znojmo 2014 Ivan & Jitka Kolombovi

Resekce kostních metastáz RCC pouze solitární meta lepší výsledky OS po 1, 2 a 5letech bylo 83%, 45%, 23% Lin PP, Mirza AN, Lewis VO et al: Patient survival after surgery for osseous metastases from renal cell carcinoma. J Bone Joint Surg Am 2007; 89: 1794-801 Znojmo 2014 Ivan & Jitka Kolombovi

Resekce jaterních metastáz RCC Jaterní metastázy RCC radikální odstranění s dobrým výsledkem stran OS po 1, 3 a 5letech bylo 82.2%, 54.3% a 38.9% (Thelen A, 2007) alternativa selektivní (Ota H, 2008) embolizace a RFA ablace Nové technologie také pro laparoskopickou intervenci Habibův skalpel (Kolombo I, 2007) Thelen A, Jonas S, Benckert C et al: Liver resection for metastases from renal cell carcinoma. Word J Surg 2007; 31: 802-7 Sengupta S, Leibovich B, Blute M et al: Surgery for metastatic renal cell cancer. World J Urol 2005; 23: 155 Ota H, Yasumoto T, Okada K, et al: A case of successful combination therapy with trans-arterial embolization, trans-arterial chemotherapy and radiofrequency ablation therapy. Gan To Kagaku Ryoho 2008 Nov;35(12):2103-5 Kolombo I, Kolombová J, Beňo P, Toběrný M a kol: Mezioborová spolupráce v urologii. Urolog. pro Praxi 2007; 8(6): 262-267 Znojmo 2014 Ivan & Jitka Kolombovi

Adrenalektomie a RCC rutinně prováděná adrenalektomie je během chirurgického výkonu zbytečná nádor větší než 7 cm; horní pól patologické postižení (CT, perioperačně) Ljunberg B, et al: EAU Guidelines on Renal Cell Carcinoma, EAU, Update 2009. www.uroweb.org Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Metastázy mozku a RCC Konveční neurochirurrgie Radiochirurgie Lekselův gama nůž Aktinoterapie Cyberknife atd. u mrcc se vyskytují asi v 4-10% hypervaskularita metastáz sklon ke krvácení Wronski M, Arbit E, Russo P, Galicich JH: Surgical resection of brain metastases from renal cel carcinoma in 50 patients. Urology 1996; 47: 187-93 Shuto T, Inomori S, Fujino H, Nagano H: Gama knife surgery for metastatic brain tumors from renal cel carcinoma. J Neurosurg 2006; 105: 555-60 Yen CP, Sheehan J, Patterson G, Steiner L: Gamma knife surgery for metastatic brain stem tumors. J Neurosurg 2006; 105: 213-9 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Timing chirurgické intervence při cílené biologické léčbě RCC Bevacizumab má dlouhý biologický poločas asi 21 dní Sunitinib, sorafenibem asi 7-10 dní M.D. Anderson Cancer Center Texas - již 24 hodin bez negat. vlivu na morbiditu Margulis V, Martin SF, Tannir N et al: Surgical morbidity associated with administration of targeted molecular therapies before cytoreductive nephrectomy or resection of locally recurent renal cell carcinoma. J Urol 2008; 180: 94-98 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Selektivní embolizace & radiofrekvenční ablace RCC sin + hematurie 66let + závažné komorbidity 1. Fáze selektivní embolizace horního pólu 2. Radiofrekvenční ablace pod CT Lokální anestézie + analgosedace Mahnken AH, et al: Percutaneous radiofrequency ablation of renal cell carcinoma: preliminary results. Acta Radiol 2005; 46: 208-214 Kolombo I, Kříž R et al: Selective embolization and radiofrequency ablation of renal mass in polymorbid and elderly patients our experience. Eur Urol 2007;2 (7), Abstract 26, Zagoria R, et al: Oncologic efficacy of CT-guided percutaneous radiofrequency ablation of renal cell carcinoma. Am J Roentgenol 2007; 189:429-436 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Selektivní embolizace & radiofrekvenční ablace RCC - dolní pól pravé ledviny (CT,PET CT) polymorbidní nemocný s neúnosným rizikem pro operační léčbu 1. fáze selektivní embolizace karcinomu Seldingerovsky v lokální anestezii Kolombo I, Kříž R et al: Selective embolization and radiofrequency ablation of renal mass in polymorbid and elderly patients our experience. Eur Urol 2007;2 (7), Abstract 26, Zagoria R, et al: Oncologic efficacy of CT-guided percutaneous radiofrequency ablation of renal cell carcinoma. Am J Roentgenol 2007; 189:429-436 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Selektivní embolizace & radiofrekvenční ablace RCC - dolní pól pravé ledviny polymorbidní nemocný s neúnosným rizikem pro operační léčbu 2. fáze radiofrekvenční ablace karcinomu CT navigovaně v lokální anestezii + sedace CT,PET CT kontrola bez viabilního Tu Kolombo I, Kříž R et al: Selective embolization and radiofrequency ablation of renal mass in polymorbid and elderly patients our experience. Eur Urol 2007;2 (7), Abstract 26, Zagoria R, et al: Oncologic efficacy of CT-guided percutaneous radiofrequency ablation of renal cell carcinoma. Am J Roentgenol 2007; 189:429-436 Znojmo 2014 Ivan & Jitka Kolombovi

Adapt study for mrcc Cluj 2015 Cavotomy & Trombectomy & Pancreatic Resection for RCC Dr. Ivan Kolombo, FEBU

Cytoredukční nefrektomie (CNE) Znojmo 4. 10. 2013 & biologická léčba First-Line Sunitinib vs IFN-α: PFS and Response Rate (RR) 750 pts. (Motzer RJ 2007) (RR ) 31% (sunitinib) versus 6% (IFN-α) (PFS) sunitinib více než dvakrát delší (11měsíců versus 5měsíců, p<0,000001) Sunitinib (SUN) 375 pts. SUN+CNE - 339 (90%) PFS 11 měsíců SUN - 36 (10%) PFS 6 měsíců (p = 0.0889) Kombinovaná analýza dvou studií II. fáze hodnotící OS u 163 (97%) pts. - sunitinib (Rosenberg JE 2007) SUN+CNE - 163 (97%) - OS 20 měsíců SUN - 5 (3%) - OS 10 měsíců (p = 0.3638) Motzer RJ, et al: Sunitinib versus interferon alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mrcc): updated results and analysis of prognostic factors. J Clin Oncol, suppl 2007; 25: abstract 5024 Rosenberg JE, Motzer RJ, Michaelson MD et al: Sunitinib therapy for patients (pts) with metastatic renal cell carcinoma (mrcc): updated results of two phase II trials and prognostic factor analysis for survival. J Clin Oncol suppl 2007; 25: abstract 5095 Ivan & Jitka Kolombovi

Cytoredukční nefrektomie (CNE) před érou biologické léčby CNE zlepšuje výsledky systémové léčby (SWOG 8949 + EORTC 30 947) základem systémové léčby mrcc byla imunoterapie (IFN α 2b) negativní imunosupresivní efekt ponechaného primárního tumoru EORTC 30 947 zlepšení přežití (OS - 17 vs 7 mths (p<0.05)) RR pouze v 6% efekt cytokinů bez provedené CNE Flanigan RC, Salmon SE, Blumenstein BA et al: Nephrectomy followed by interferon α-2b compared with interferon α-2b alone for metastatic renal cell cancer. N Engl J Med 2001; 345: 1655-9 Mickisch GH, et al: Radical nephrectomy plus interferon α-based immunotherapy compared with interferon α alone for metastatic renal cell carcinoma: a randomized trial. Lancet 2001; 358: 966-70 Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Biologická léčba nový zlatý standard systémové léčby RCC Sunitinib statisticky významně prodlužuje dobu do progrese onemocnění (PFS progression-free survival), >2x delší (11měsíců versus 5měsíců, p<0,000001). Sunitinib jasně účinnější v 1.linii systémové léčby u mrcc než konvenční imunoterapie. Motzer RJ, Hutson TE, Tomczak P et al: Sunitinib versus interferon alfa in metastatic renal cell carcinoma. N Engl J Med 2007; 356: 115-24 Znojmo 2014 Ivan & Jitka Kolombovi

Biologická léčba nový zlatý standard systémové léčby RCC Escudier B, Eisen T at al. TARGET Study Group.: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):125-134 Escudier B, Koralewski P,at al.: A randomised, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-{alpha}2a vs placebo/ interferon-{alpha}2a as first-line therapy in metastatic renal cell carcinoma. J Clin Oncol 2007; 25:3 Hudes G, Carducci M, et al: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356: 2271-81 Motzer RJ, Escudier B, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomized, placebo-controlled phase III trial. Lancet 2008;372:449 56. Znojmo 4. 10. 2013 Ivan & Jitka Kolombovi

Salvage Surgery & Fast Track Our Experience (2014) - ICS 2015 Salvage Surgery & Fast Track Dr. Ivan Kolombo, FEBU 60