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Journal of Cancer Research and Clinical Oncology

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01-11-2016 | Original Article – Clinical Oncology

Impact of metastasectomy on prognosis in patients treated with targeted therapy for metastatic renal cell carcinoma

Authors: Dalsan You, Chunwoo Lee, In Gab Jeong, Cheryn Song, Jae-Lyun Lee, Bumsik Hong, Jun Hyuk Hong, Hanjong Ahn, Choung-Soo Kim

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2016

Abstract

Purpose

We evaluated the value of metastasectomy in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).

Methods

The medical records of 325 patients who presented with mRCC were reviewed; among these patients, 33 underwent complete metastasectomy followed by targeted therapy (complete metastasectomy group), 29 underwent incomplete metastasectomy followed by targeted therapy (incomplete metastasectomy group), and 263 treated with targeted therapy alone (non-metastasectomy group). We estimated progression-free and overall survivals using Kaplan–Meier curves. A Cox proportional hazards regression model was used to estimate the prognostic significance of metastasectomy.

Results

Clinicopathological variables did not differ among the three groups except for age, history of nephrectomy, type of metastasis, the International Metastatic Renal Cell Carcinoma Database Consortium risk groups, histology, and bone metastasis. The median progression-free survivals were 29.5, 18.8, and 14.8 months in the complete, incomplete, and non-metastasectomy groups (p < 0.001). Complete metastasectomy (hazard ratio 0.431, p = 0.001) was an independent predictor of disease progression, along with targeted agents, risk groups, sarcomatoid feature, and number of metastatic sites. The median overall survivals were 92.5, 29.6, and 23.5 months in the complete, incomplete, and non-metastasectomy groups (p < 0.001). Complete metastasectomy (hazard ratio 0.378, p = 0.001) was an independent predictor of overall survival, along with targeted agents, type of metastasis, risk groups, sarcomatoid feature, and number of metastatic sites.

Conclusions

Complete metastasectomy performed before targeted therapy might improve progression-free and overall survivals in patients with mRCC.

Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML (2011) Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer 117:2873–2882CrossRefPubMed

Barney JD, Churchill BM (1939) Adenocarcinoma of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy. J Urol 42:269–276

Choueiri TK, Schutz FA, Je Y, Rosenberg JE, Bellmunt J (2010) Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and metaanalysis of clinical trials. J Clin Oncol 28:2280–2285CrossRefPubMed

Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG, McDermott DF, Rini BI, Heng DY (2011) The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol 185:60–66CrossRefPubMed

Dabestani S, Marconi L, Hofmann F, Stewart F, Lam TB, Canfield SE, Staehler M, Powles T, Ljungberg B, Bex A (2014) Local treatments for metastases of renal cell carcinoma: a systematic review. Lancet Oncol 15:e549–e561CrossRefPubMed

Daliani DD, Tannir NM, Papandreou CN, Wang X, Swisher S, Wood CG, Swanson DA, Logothetis CJ, Jonasch E (2009) Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma. BJU Int 104:456–460CrossRefPubMedPubMedCentral

Ebos JM, Lee CR, Christensen JG, Mutsaers AJ, Kerbel RS (2007) Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc Natl Acad Sci USA 104:17069–17074CrossRefPubMedPubMedCentral

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM, TARGET Study Group (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMed

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefPubMed

Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345:1655–1659CrossRefPubMed

Flanigan RC, Campbell SC, Clark JI, Picken MM (2003) Metastatic renal cell carcinoma. Curr Treat Options Oncol 4:385–390CrossRefPubMed

Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF (2010) Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial. Lancet 375:641–648CrossRefPubMedPubMedCentral

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 (2014) Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 66:704–710CrossRefPubMed

Je Y, Schutz FA, Choueiri TK (2009) Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncol 10:967–974CrossRefPubMed

Karam JA, Rini BI, Varella L, Garcia JA, Dreicer R, Choueiri TK, Jonasch E, Matin SF, Campbell SC, Wood CG, Tannir NM (2011) Metastasectomy after targeted therapy in patients with advanced renal cell carcinoma. J Urol 185:439–444CrossRefPubMed

Kim DY, Karam JA, Wood CG (2014) Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy. World J Urol 32:631–642CrossRefPubMed

Leibovich BC, Cheville JC, Lohse CM, Zincke H, Frank I, Kwon ED, Merchan JR, Blute ML (2005) A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. J Uro 174:1759–1763CrossRef

Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R, European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358:966–970CrossRefPubMed

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMed

Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ (2014) Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 32:2765–2772CrossRefPubMed

Pazopanib hydrochloride in treating patients with metastatic kidney cancer who have no evidence of disease after surgery. http://www.clinicaltrials.gov/ct2/show/NCT01575548. Accessed 5 April 2015

Procopio G, Verzoni E, Biondani P, Grassi P, Testa I, Garanzini E, de Braud F (2014) Rationale and protocol of RESORT, a randomized, open-label, multicenter phase II study to evaluate the efficacy of sorafenib in patients with advanced renal cell carcinoma after radical resection of the metastases. Tumori 100:e28–e30PubMed

Rexer H (2012) Urgent patient admission to Working Group for Urological Oncology (AUO) studies on metastasized renal cell carcinoma needed: prospective randomized multicenter phase II study on resection of pulmonary metastases in clear cell renal cell carcinoma ± adjuvant sunitinib therapy over 1 year (SMAT - AN 20/04 of the AUO). Urologe A 51:252–253CrossRefPubMed

Rini BI, Shaw V, Rosenberg JE, Kim ST, Chen I (2006) Patients with metastatic renal cell carcinoma with long-term disease-free survival after treatment with sunitinib and resection of residual metastases. Clin Genitourin Cancer 5:232–234CrossRefPubMed

Shuch B, Riggs SB, LaRochelle JC, Kabbinavar FF, Avakian R, Pantuck AJ, Patard JJ, Belldegrun AS (2008) Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm. BJU Int 102:692–696CrossRefPubMed

Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068CrossRefPubMed

Thomas AA, Rini BI, Stephenson AJ, Garcia JA, Fergany A, Krishnamurthi V, Novick AC, Gill IS, Klein EA, Zhou M, Campbell SC (2009) Surgical resection of renal cell carcinoma after targeted therapy. J Urol 182:881–886CrossRefPubMed

Wahlgren T, Harmenberg U, Sandström P, Lundstam S, Kowalski J, Jakobsson M, Sandin R, Ljungberg B (2013) Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000–2008). Br J Cancer 108:1541–1549CrossRefPubMedPubMedCentral

You D, Jeong IG, Song C, Lee JL, Hong B, Hong JH, Ahn H, Kim CS (2015) Analysis of pre-operative variables for identifying patients who might benefit from upfront cytoreductive nephrectomy for metastatic renal cell carcinoma in the targeted therapy era. Jpn J Clin Oncol 45:96–102CrossRefPubMed

Yu X, Wang B, Li X, Lin G, Zhang C, Yang Y, Fang D, Song Y, He Z, Zhou L (2015) The Significance of Metastasectomy in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy. Biomed Res Int 2015:176373PubMedPubMedCentral

Title: Impact of metastasectomy on prognosis in patients treated with targeted therapy for metastatic renal cell carcinoma
Authors: Dalsan You
Chunwoo Lee
In Gab Jeong
Cheryn Song
Jae-Lyun Lee
Bumsik Hong
Jun Hyuk Hong
Hanjong Ahn
Choung-Soo Kim
Publication date: 01-11-2016
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2016
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2217-1

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