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Journal of Cancer Research and Clinical Oncology

, Volume 142, Issue 11, pp 2331–2338 | Cite as

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

  • Dalsan You
  • Chunwoo Lee
  • In Gab Jeong
  • Cheryn Song
  • Jae-Lyun Lee
  • Bumsik Hong
  • Jun Hyuk Hong
  • Hanjong Ahn
  • Choung-Soo KimEmail author
Original Article – Clinical Oncology

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.

Keywords

Renal cell carcinoma Metastasis Metastasectomy Molecular targeted therapy Prognosis 

Notes

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Institutional Review Board of the Asan Medical Center (2015–0808). All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of the Asan Medical Center and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

The Institutional Review Board of the Asan Medical Center waived the requirement for informed consent because of the retrospective design of this study.

References

  1. 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 117:2873–2882CrossRefPubMedGoogle Scholar
  2. Barney JD, Churchill BM (1939) Adenocarcinoma of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy. J Urol 42:269–276Google Scholar
  3. 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 28:2280–2285CrossRefPubMedGoogle Scholar
  4. 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 185:60–66CrossRefPubMedGoogle Scholar
  5. 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–e561CrossRefPubMedGoogle Scholar
  6. 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 104:456–460CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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 104:17069–17074CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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 356:125–134CrossRefPubMedGoogle Scholar
  9. 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–E386CrossRefPubMedGoogle Scholar
  10. 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 345:1655–1659CrossRefPubMedGoogle Scholar
  11. Flanigan RC, Campbell SC, Clark JI, Picken MM (2003) Metastatic renal cell carcinoma. Curr Treat Options Oncol 4:385–390CrossRefPubMedGoogle Scholar
  12. 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 375:641–648CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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 66:704–710CrossRefPubMedGoogle Scholar
  14. 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 10:967–974CrossRefPubMedGoogle Scholar
  15. 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 185:439–444CrossRefPubMedGoogle Scholar
  16. Kim DY, Karam JA, Wood CG (2014) Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy. World J Urol 32:631–642CrossRefPubMedGoogle Scholar
  17. 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 174:1759–1763CrossRefGoogle Scholar
  18. 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 358:966–970CrossRefPubMedGoogle Scholar
  19. 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 356:115–124CrossRefPubMedGoogle Scholar
  20. 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 32:2765–2772CrossRefPubMedGoogle Scholar
  21. 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
  22. 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–e30PubMedGoogle Scholar
  23. 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 51:252–253CrossRefPubMedGoogle Scholar
  24. 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 5:232–234CrossRefPubMedGoogle Scholar
  25. 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 102:692–696CrossRefPubMedGoogle Scholar
  26. 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 28:1061–1068CrossRefPubMedGoogle Scholar
  27. 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 182:881–886CrossRefPubMedGoogle Scholar
  28. 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 108:1541–1549CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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 45:96–102CrossRefPubMedGoogle Scholar
  30. 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 2015:176373PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Dalsan You
    • 1
  • Chunwoo Lee
    • 2
  • In Gab Jeong
    • 1
  • Cheryn Song
    • 1
  • Jae-Lyun Lee
    • 3
  • Bumsik Hong
    • 1
  • Jun Hyuk Hong
    • 1
  • Hanjong Ahn
    • 1
  • Choung-Soo Kim
    • 1
    Email author
  1. 1.Department of Urology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Department of UrologyGyeongsang National University Changwon Hospital, Gyeongsang National University School of MedicineChangwonKorea
  3. 3.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

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