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Does the onset of bone metastasis in sunitinib-treated renal cell carcinoma patients impact the overall survival?

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Abstract

Purpose

To evaluate the impact of bone metastasis (BM) onset toward prognosis in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib.

Methods

mRCC patients with BM and sunitinib as first targeted therapy between May 2005 and December 2012 were retrospectively analyzed. Patients with synchronous (s) BM or metachronous (m) BM were compared with regard to treatment and outcome [time to clinical progression (TTcP), overall survival (OS), skeletal-related events (SRE)]. Descriptive statistics, Kaplan–Meier estimation of TTcP and OS, Cox regression analyses, and a landmark analysis were administered.

Results

BM was identified in 127 mRCC patients; thereof, 82 sunitinib-treated patients were analyzed [sBM n = 57 (69.5 %), mBM n = 25 (30.5 %)]. Higher tumor grading (p = 0.029), male predominance (p = 0.02), and less second-line therapy (p = 0.001) were detected in sBM compared to mBM. SRE remained similar between subgroups (p = 0.462). TTcP during sunitinib was similar [median sBM 8.1 (95 % CI 3.9–12.3) vs. mBM 8.7 (95 % CI 2.7–14.8) months, p = 0.903]. OS remained significantly inferior in sBM patients compared to mBM [median sBM 21.1 (95 % CI 16–26.2) months vs. mBM 38.5 (95 % CI 15–62) months, p = 0.001], which was confirmed by landmark analyses at 1.5, 3, 6, 9, and 12 months. However, OS after occurrence of BM was similar in both groups [median sBM 24.2 (95 % CI 17.3–31.1) months vs. mBM 17.2 (95 % CI 8.4–26) months, p = 0.519].

Conclusions

mBM is associated with an improved OS compared to sBM in mRCC with sunitinib treatment, despite similar efficacy of sunitinib treatment in both groups of patients.

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References

  1. McKay RR, Lin X, Perkins JJ, Heng DY, Simantov R, Choueiri TK (2014) Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma. Eur Urol. doi:10.1016/j.eururo.2014.02.040

    PubMed Central  Google Scholar 

  2. Patil S, Figlin RA, Hutson TE, Michaelson MD, Negrier S, Kim ST, Huang X, Motzer RJ (2011) Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22(2):295–300. doi:10.1093/annonc/mdq342

    Article  CAS  PubMed  Google Scholar 

  3. Toyoda Y, Shinohara N, Harabayashi T, Abe T, Akino T, Sazawa A, Nonomura K (2007) Survival and prognostic classification of patients with metastatic renal cell carcinoma of bone. Eur Urol 52(1):163–168. doi:10.1016/j.eururo.2006.10.060

    Article  PubMed  Google Scholar 

  4. McKay RR, Kroeger N, Xie W, Lee JL, Knox JJ, Bjarnason GA, MacKenzie MJ, Wood L, Srinivas S, Vaishampayan UN, Rha SY, Pal SK, Donskov F, Tantravahi SK, Rini BI, Heng DY, Choueiri TK (2014) Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. Eur Urol 65(3):577–584. doi:10.1016/j.eururo.2013.08.012

    Article  PubMed  Google Scholar 

  5. Motzer RJ, Escudier B, Bukowski R, Rini BI, Hutson TE, Barrios CH, Lin X, Fly K, Matczak E, Gore ME (2013) Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma. Br J Cancer 108(12):2470–2477. doi:10.1038/bjc.2013.236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Santini D, Procopio G, Porta C, Ibrahim T, Barni S, Mazzara C, Fontana A, Berruti A, Berardi R, Vincenzi B, Ortega C, Ottaviani D, Carteni G, Lanzetta G, Virzi V, Santoni M, Silvestris N, Satolli MA, Collova E, Russo A, Badalamenti G, Fedeli SL, Tanca FM, Adamo V, Maiello E, Sabbatini R, Felici A, Cinieri S, Tonini G, Bracarda S (2013) Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey. PLoS One 8(12):e83026. doi:10.1371/journal.pone.0083026

    Article  PubMed  PubMed Central  Google Scholar 

  7. Molina AM, Jia X, Feldman DR, Hsieh JJ, Ginsberg MS, Velasco S, Patil S, Motzer RJ (2013) Long-term response to sunitinib therapy for metastatic renal cell carcinoma. Clin Genitourin Cancer 11(3):297–302. doi:10.1016/j.clgc.2013.04.001

    Article  PubMed  PubMed Central  Google Scholar 

  8. Beuselinck B, Oudard S, Rixe O, Wolter P, Blesius A, Ayllon J, Elaidi R, Schoffski P, Barrascout E, Morel A, Escudier B, Lang H, Zucman-Rossi J, Medioni J (2011) Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol 22(4):794–800. doi:10.1093/annonc/mdq554

    Article  CAS  PubMed  Google Scholar 

  9. Althausen P, Althausen A, Jennings LC, Mankin HJ (1997) Prognostic factors and surgical treatment of osseous metastases secondary to renal cell carcinoma. Cancer 80(6):1103–1109. doi:10.1002/(SICI)1097-0142(19970915)80:6<1103:AID-CNCR13>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  10. Thompson IM, Shannon H, Ross G Jr, Montie J (1975) An analysis of factors affecting survival in 150 patients with renal carcinoma. J Urol 114(5):694–696

    CAS  PubMed  Google Scholar 

  11. Smith MR (2005) Zoledronic acid to prevent skeletal complications in cancer: corroborating the evidence. Cancer Treat Rev 31(Suppl 3):19–25. doi:10.1016/j.ctrv.2005.09.004

    Article  PubMed  Google Scholar 

  12. Keizman D, Ish-Shalom M, Pili R, Hammers H, Eisenberger MA, Sinibaldi V, Boursi B, Maimon N, Gottfried M, Hayat H, Peer A, Kovel S, Sella A, Berger R, Carducci MA (2012) Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma. Eur J Cancer 48(7):1031–1037. doi:10.1016/j.ejca.2012.02.050

    Article  CAS  PubMed  Google Scholar 

  13. Sahi C, Knox JJ, Clemons M, Joshua AM, Broom R (2010) Renal cell carcinoma bone metastases: clinical advances. Ther Adv Med Oncol 2(2):75–83. doi:10.1177/1758834009358417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Santoni M, Conti A, Procopio G, Porta C, Ibrahim T, Barni S, Guida FM, Fontana A, Berruti A, Berardi R, Massari F, Vincenzi B, Ortega C, Ottaviani D, Carteni G, Lanzetta G, De Lisi D, Silvestris N, Satolli MA, Collova E, Russo A, Badalamenti G, Luzi Fedeli S, Tanca FM, Adamo V, Maiello E, Sabbatini R, Felici A, Cinieri S, Montironi R, Bracarda S, Tonini G, Cascinu S, Santini D (2015) Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res 34:10. doi:10.1186/s13046-015-0122-0

    Article  PubMed  PubMed Central  Google Scholar 

  15. Heng DY, Xie W, Bjarnason GA, Vaishampayan U, Tan MH, Knox J, Donskov F, Wood L, Kollmannsberger C, Rini BI, Choueiri TK (2011) Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy. Cancer 117(12):2637–2642. doi:10.1002/cncr.25750

    Article  PubMed  Google Scholar 

  16. Halabi S, Vogelzang NJ, Ou SS, Owzar K, Archer L, Small EJ (2009) Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer. J Clin Oncol 27(17):2766–2771. doi:10.1200/JCO.2008.18.9159

    Article  PubMed  PubMed Central  Google Scholar 

  17. Anderson JR, Cain KC, Gelber RD, Gelman RS (1985) Analysis and interpretation of the comparison of survival by treatment outcome variables in cancer clinical trials. Cancer Treat Rep 69(10):1139–1146

    CAS  PubMed  Google Scholar 

  18. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S, Venner P, Knox JJ, Chi KN, Kollmannsberger C, McDermott DF, Oh WK, Atkins MB, Bukowski RM, Rini BI, Choueiri TK (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27(34):5794–5799. doi:10.1200/JCO.2008.21.4809

    Article  CAS  PubMed  Google Scholar 

  19. McKay RR, Lin X, Perkins JJ, Heng DY, Simantov R, Choueiri TK (2014) Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma. Eur Urol 66(3):502–509. doi:10.1016/j.eururo.2014.02.040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Seidel C, Busch J, Weikert S, Steffens S, Fenner M, Ganser A, Grunwald V (2012) Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma. Eur J Cancer 48(7):1023–1030. doi:10.1016/j.ejca.2012.02.048

    Article  CAS  PubMed  Google Scholar 

  21. Onishi T, Ohishi Y, Iizuka N, Makino H (1995) Study on the pathological grade in the primary and distant metastatic lesions of renal cell carcinoma. Hinyokika Kiyo 41(12):959–963

    CAS  PubMed  Google Scholar 

  22. Segal E, Pan H, Ofek P, Udagawa T, Kopeckova P, Kopecek J, Satchi-Fainaro R (2009) Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PLoS One 4(4):e5233. doi:10.1371/journal.pone.0005233

    Article  PubMed  PubMed Central  Google Scholar 

  23. Saylor PJ, Armstrong AJ, Fizazi K, Freedland S, Saad F, Smith MR, Tombal B, Pienta K (2013) New and emerging therapies for bone metastases in genitourinary cancers. Eur Urol 63(2):309–320. doi:10.1016/j.eururo.2012.10.007

    Article  CAS  PubMed  Google Scholar 

  24. Kominsky SL, Doucet M, Thorpe M, Weber KL (2008) MMP-13 is over-expressed in renal cell carcinoma bone metastasis and is induced by TGF-beta1. Clin Exp Metastasis 25(8):865–870. doi:10.1007/s10585-008-9202-2

    Article  CAS  PubMed  Google Scholar 

  25. Joeckel E, Haber T, Prawitt D, Junker K, Hampel C, Thuroff JW, Roos FC, Brenner W (2014) High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor. Mol Cancer 13:42. doi:10.1186/1476-4598-13-42

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mikami S, Oya M, Mizuno R, Kosaka T, Katsube K, Okada Y (2014) Invasion and metastasis of renal cell carcinoma. Med Mol Morphol 47(2):63–67. doi:10.1007/s00795-013-0064-6

    Article  CAS  PubMed  Google Scholar 

  27. Satcher RL, Pan T, Cheng CJ, Lee YC, Lin SC, Yu G, Li X, Hoang AG, Tamboli P, Jonasch E, Gallick GE, Lin SH (2014) Cadherin-11 in renal cell carcinoma bone metastasis. PLoS One 9(2):e89880. doi:10.1371/journal.pone.0089880

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kominsky SL, Abdelmagid SM, Doucet M, Brady K, Weber KL (2008) Macrophage inflammatory protein-1 delta: a novel osteoclast stimulating factor secreted by renal cell carcinoma bone metastasis. Cancer Res 68(5):1261–1266. doi:10.1158/0008-5472.CAN-07-6122

    Article  CAS  PubMed  Google Scholar 

  29. Giampieri S, Manning C, Hooper S, Jones L, Hill CS, Sahai E (2009) Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol 11(11):1287–1296. doi:10.1038/ncb1973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Weber KL, Doucet M, Price JE, Baker C, Kim SJ, Fidler IJ (2003) Blockade of epidermal growth factor receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice. Cancer Res 63(11):2940–2947

    CAS  PubMed  Google Scholar 

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Authors contribution

CS, PI, VG, JB, and CWR treated the patients and assessed the data. Data collections were assessed by CS, JK, JB, and PI. Statistics were calculated by AT, JK, PI. The manuscript was written, discussed and critically revised by PI, JK, AT, JB, CS, CWR, AG, and VG. The study was coordinated by VG.

Declaration

Patient treatment was performed after signing written informed consent, and patient analysis was done in an anonymized manner, in concordance with local ethic committee recommendation as well as according to the Declaration of Helsinki in the latest revised version.

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    Authors and Affiliations

    1. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany

      P. Ivanyi, J. Koenig, A. Trummer, C. W. Reuter, A. Ganser & V. Grünwald

    2. Clinic of Urology, University Hospital Berlin, Charité, Berlin, Germany

      J. F. Busch

    3. Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Medical Center Eppendorf, Hamburg, Germany

      C. Seidel

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    1. P. Ivanyi
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    Correspondence to V. Grünwald.

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    Conflict of interest

    PI: Advisory role: Novartis, GSK, Bayer; JK: None; AT: None; JB: Advisor to Pfizer, Novartis, Mologen and Bayer; lectures for Pfizer and Astellas; CS: None; CWR: None; AG: None; CG: None; VG: Honoraria: Novartis, Pfizer, GSK, BMS. Advisory role: Novartis, Pfizer, GSK, BMS, MSD, Bayer.

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    P. Ivanyi and J. Koenig have contributed equally to this work.

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    Ivanyi, P., Koenig, J., Trummer, A. et al. Does the onset of bone metastasis in sunitinib-treated renal cell carcinoma patients impact the overall survival?. World J Urol 34, 909–915 (2016). https://doi.org/10.1007/s00345-015-1707-0

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    • DOI: https://doi.org/10.1007/s00345-015-1707-0

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