Objectives: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. Methods: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. Results: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17–39 months) and 42 months (95% CI 30–54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. Conclusions: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.

Keywords:
Renal cell carcinoma, Tumor thrombus, Neoadjuvant therapy, Prognosis, Sunitinib, Sorafenib
1.
Kirkali Z, Van Poppel H: A critical analysis of surgery for kidney cancer with vena cava invasion. Eur Urol 2007; 52: 658–662.
2.
Haferkamp A, Bastian PJ, Jakobi H, Pritsch M, Pfitzenmaier J, Albers P, Hallscheidt P, Muller SC, Hohenfellner M: Renal cell carcinoma with tumor thrombus extension into the vena cava: prospective long-term followup. J Urol 2007; 177: 1703–1708.
3.
Tang Q, Song Y, Li X, Meng M, Zhang Q, Wang J, He Z, Zhou L: Prognostic outcomes and risk factors for patients with renal cell carcinoma and venous tumor thrombus after radical nephrectomy and thrombectomy: the prognostic significance of venous tumor thrombus level. Biomed Res Int 2015; 2015: 163423.
4.
Tornberg SV, Nisen H, Visapaa H, Kilpelainen TP, Jarvinen R, Mirtti T, Kantonen I, Simpanen J, Bono P, Taari K, Jarvinen P: Outcome of surgery for patients with renal cell carcinoma and tumour thrombus in the era of modern targeted therapy. Scand J Urol 2016; 50: 380–386.
5.
Mager R, Daneshmand S, Evans CP, Palou J, Martinez-Salamanca JI, Master VA, McKiernan JM, Libertino JA, Haferkamp A; International Renal Cell Carcinoma-Venous Thrombus Consortium, Haferkamp A, Capitanio U, Carballido JA, Chantada V, Chromecki T, Ciancio G, Daneshmand S, Evans CP, Gontero P, Gonzalez J, Hohenfellner M, Huang WC, Koppie TM, Libertino JA, Espinos EL, Lorentz A, Martinez-Salamanca JI, Master VA, McKiernan JM, Montorsi F, Novara G, O'Malley P, Pahernik S, Palou J, Moreno JL, Pruthi RS, Faba OR, Russo P, Scherr DS, Shariat SF, Spahn M, Terrone C, Tilki D, Vazquez-Martul D, Donoso CV, Vergho D, Wallen EM, Zigeuner R: Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival. J Surg Oncol 2016; 114: 764–768.
6.
Nandagopal L, Naik G, Sonpavde G: Overview of current and future adjuvant therapy for high-risk localized renal cell carcinoma. Curr Treat Options Oncol 2018; 19: 2.
7.
Bindayi A, Hamilton ZA, McDonald ML, Yim K, Millard F, McKay RR, Campbell SC, Rini BI, Derweesh IH: Neoadjuvant therapy for localized and locally advanced renal cell carcinoma. Urol Oncol 2018; 36: 31–37.
8.
Zhang Y, Li Y, Deng J, Ji Z, Yu H, Li H: Sorafenib neoadjuvant therapy in the treatment of high risk renal cell carcinoma. PLoS One 2015; 10:e0115896.
9.
Sassa N, Kato M, Funahashi Y, Maeda M, Inoue S, Gotoh M: Efficacy of pre-surgical axitinib for shrinkage of inferior vena cava thrombus in a patient with advanced renal cell carcinoma. Jpn J Clin Oncol 2014; 44: 370–373.
10.
Cost NG, Delacroix SE Jr, Sleeper JP, Smith PJ, Youssef RF, Chapin BF, Karam JA, Culp S, Abel EJ, Brugarolas J, Raj GV, Sagalowsky AI, Wood CG, Margulis V: The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus. Eur Urol 2011; 59: 912–918.
11.
David KA, Milowsky MI, Ritchey J, Carroll PR, Nanus DM: Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base. J Urol 2007; 178: 451–454.
12.
International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK: International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011; 29: 2171–2177.
13.
Hermans TJ, Voskuilen CS, van der Heijden MS, Schmitz-Drager BJ, Kassouf W, Seiler R, Kamat AM, Grivas P, Kiltie AE, Black PC, van Rhijn BW: Neoadjuvant treatment for muscle-invasive bladder cancer: the past, the present, and the future. Urol Oncol 2017:pii:S1078-1439(17)30551-3.
14.
Blute ML, Leibovich BC, Lohse CM, Cheville JC, Zincke H: The Mayo Clinic experience with surgical management, complications and outcome for patients with renal cell carcinoma and venous tumour thrombus. BJU Int 2004; 94: 33–41.
15.
Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds): AJCC Cancer Staging Manual (ed 7). New York, NY, Springer, 2010.
16.
Heng DYC, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, Mackenzie M, Wood L, Donskov F, Tan MH, Rha SY, Agarwal N, Kollmannsberger C, Rini BI, Choueiri TK: External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol 2013; 14: 141–148.
17.
Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman C: CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13: 176–181.
18.
Dindo D, Demartines N, Clavien PA: Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–213.
19.
Karam JA, Devine CE, Urbauer DL, Lozano M, Maity T, Ahrar K, Tamboli P, Tannir NM, Wood CG: Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma. Eur Urol 2014; 66: 874–880.
20.
Karam JA, Devine CE, Fellman BM, Urbauer DL, Abel EJ, Allaf ME, Bex A, Lane BR, Thompson RH, Wood CG: Variability of inter-observer agreement on feasibility of partial nephrectomy before and after neoadjuvant axitinib for locally advanced renal cell carcinoma (RCC): independent analysis from a phase II trial. BJU Int 2016; 117: 629–635.
21.
Dey S, Peabody HN, Noyes SL, Lane BR: Neoadjuvant targeted molecular therapy before renal surgery. Urol Clin N Am 2017; 44: 289–303.
22.
Borregales LD, Adibi M, Thomas AZ, Wood CG, Karam JA: The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma. Ther Adv Urol 2016; 8: 130–141.
23.
Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, Bjarnason GA, Pal SK, Kollmannsberger CK, Yuasa T, Srinivas S, Donskov F, Bamias A, Wood LA, Ernst DS, Agarwal N, Vaishampayan UN, Rha SY, Kim JJ, Choueiri TK: Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 2014; 66: 704–710.
24.
Bigot P, Fardoun T, Bernhard JC, Xylinas E, Berger J, Roupret M, Beauval JB, Lagabrielle S, Lebdai S, Ammi M, Baumert H, Escudier B, Grenier N, Hetet JF, Long JA, Paparel P, Rioux-Leclercq N, Soulie M, Azzouzi AR, Bensalah K, Patard JJ: Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful? World J Urol 2014; 32: 109–114.
25.
de Azevedo C, Thuler LC, de Mello MJ, de Oliveira Lima JT, da Fonte AL, Fontao DF, Carneiro VC, Chang TM, Ferreira CG: Phase II trial of neoadjuvant chemotherapy followed by chemoradiation in locally advanced cervical cancer. Gynecologic Oncol 2017; 146: 560–565.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.