Concomitant radiotherapy and transarterial chemoembolization reduce skeletal-related events related to bone metastases from renal cell carcinoma

  • Joichi HeiannaEmail author
  • Wataru Makino
  • Takuro Ariga
  • Kazuki Ishikawa
  • Takeaki Kusada
  • Hitoshi Maemoto
  • Masafumi Toguchi
  • Junji Ito
  • Masato Goya
  • Minoru Miyazato
  • Yuko Iraha
  • Sadayuki Murayama



The purpose of this study was to compare the efficacy of radiotherapy (RT) combined with transcatheter arterial chemoembolization (TACE) with RT alone for the treatment of bone metastases from renal cell carcinoma (RCC).


We included in this retrospective study 25 RCC patients (28 bone metastases), who were treated with RT at our institution. Patients were divided into two groups: patients treated with RT alone (monotherapy group; n = 17) and those treated with RT combined with TACE (combined therapy group; n = 11). The administered median RT dose was 30 Gy in 10 fractions. Anti-cancer agents used in TACE were cisplatin (median dose, 50 mg) and carboplatin (median dose, 240 mg) for patients with reduced renal function. We evaluated the objective response, post-RT-skeletal-related event (PR-SRE)–free rate, and adverse events associated with treatment for each group.


The objective response rates for bone metastases in the monotherapy and combined therapy groups were 33% and 82%, respectively (p = 0.009). The 2-year PR-SRE-free rate in the monotherapy and combined therapy groups was 41.8% and 100%, respectively (p = 0.009). The objective response and PR-SRE-free rates were significantly superior in the combined therapy than in the monotherapy group. There were no significant differences in adverse events or survival between the two groups.


RT combined with TACE is a promising treatment for bone metastases from RCC, as it results in higher objective response, and PR-SRE-free rates compared with RT alone.

Key Points

• Skeletal-related events (SREs) are common in patients with bone metastases from renal cell carcinoma (RCC).

• Radiotherapy (RT) provides pain relief in patients with bone metastases from RCC, but rarely achieves objective response.

• Combination of RT with transcatheter arterial chemoembolization results in higher objective response and post-RT-SRE-free rates compared with RT alone and is a promising treatment for bone metastases from RCC, as it.


Renal cell carcinoma Bone neoplasm Therapeutic embolization Radiotherapy 



Bone-modifying agent


Complete response


Computed tomography


Immune checkpoint inhibitor


Magnetic resonance imaging


Molecularly targeted therapy


Progressive disease


Partial response


Post-radiotherapy-skeletal-related event


Quality of life


Renal cell carcinoma




Stable response


Skeletal-related event


Transcatheter arterial chemoembolization


Transcatheter arterial embolization


Funding information

This study was supported by a grant-in-aid of the Uruma Fund for the Promotion of Science.

Compliance with ethical standards


The scientific guarantor of this publication is Sadayuki Murayama.

Conflict of interest

The authors declare that they have no conflict of interest.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• observational

• performed at one institution


  1. 1.
    Woodward E, Jagdev S, McParland L et al (2011) Skeletal complications and survival in renal cancer patients with bone metastases. Bone 48:160–166CrossRefGoogle Scholar
  2. 2.
    Bianchi M, Sun M, Jeldres C et al (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23:973–980CrossRefGoogle Scholar
  3. 3.
    Beuselinck B, Oudard S, Rixe O et al (2011) Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol 22:794–800CrossRefGoogle Scholar
  4. 4.
    Santoni M, Conti A, Procopio G et al (2015) Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? J Exp Clin Cancer Res. CrossRefGoogle Scholar
  5. 5.
    McKay RR, Kroeger N, Xie W et al (2014) Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. Eur Urol 65:577–584CrossRefGoogle Scholar
  6. 6.
    Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590CrossRefGoogle Scholar
  7. 7.
    Escudier B, Eiseen T, Stadler WM et al (2009) Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 27:3312–3318CrossRefGoogle Scholar
  8. 8.
    Calvo E, Escudier B, Motzer RJ et al (2012) Everolimus in metastatic renal cell carcinoma: subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 48:333–339CrossRefGoogle Scholar
  9. 9.
    Bedke J, Stuhler V, Stenzl A, Brehmer B (2018) Immunotherapy for kidney cancer: status quo and the future. Curr Opin Urol 28:8–14CrossRefGoogle Scholar
  10. 10.
    Teyssonneau D, Gross-Goupil M, Domblides C et al (2018) Treatment of spinal metastases in renal cell carcinoma: a critical review. Crit Rev Oncol Hematol 125:19–29CrossRefGoogle Scholar
  11. 11.
    Lipton A, Zheng M, Seaman J (2003) Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 98:962–969CrossRefGoogle Scholar
  12. 12.
    Jung ST, Ghert MA, Harrelson JM, Scully SP (2003) Treatment of osseous metastases in patients with renal cell carcinoma. Clin Orthop Relat Res 409:223–231CrossRefGoogle Scholar
  13. 13.
    Lee J, Hodgson D, Chow E et al (2005) A phase II trial of palliative radiotherapy for metastatic renal cell carcinoma. Cancer 104:1894–1900CrossRefGoogle Scholar
  14. 14.
    Kijima T, Fujii Y, Suyama T et al (2008) Radiotherapy to bone metastases from renal cell carcinoma with or without zoledronate. BJU Int 103:620–624CrossRefGoogle Scholar
  15. 15.
    Hosaka S, Katagiri H, Niwakawa M et al (2018) Radiotherapy combined with zoledronate can reduce skeletal-related events in renal cell carcinoma patients with bone metastasis. Int J Clin Oncol 23:1127–1133CrossRefGoogle Scholar
  16. 16.
    Sun S, Lang EV (1998) Bone metastases from renal cell carcinoma: preoperative embolization. J Vasc Interv Radiol 9:263–269CrossRefGoogle Scholar
  17. 17.
    Wirbel RJ, Roth R, Schlte M, Kramann B, Mutschler W (2005) Preoperative embolization in spinal and pelvic metastases. J Orthop Sci 10:253–257CrossRefGoogle Scholar
  18. 18.
    Gupta P, Gamanagatti S (2012) Preoperative transarterial embolisation in bone tumors. World J Radiol 4:186–192CrossRefGoogle Scholar
  19. 19.
    Radeleff B, Eiers M, Lopez-Benitez R et al (2006) Transarterial embolization of primary and secondary tumors of the skeletal system. Eur J Radiol 58:68–75CrossRefGoogle Scholar
  20. 20.
    Forauer AR, Kent E, Cwikiel W, Esper P, Redman B (2007) Selective palliative transcatheter embolization of bony metastases from renal cell carcinoma. Acta Oncol 46:1012–1018CrossRefGoogle Scholar
  21. 21.
    Nagata Y, Mitsumori M, Okajima K et al (1998) Transcatheter arterial embolization for malignant osseous and soft tissue sarcomas. II. Clinical results. Cardiovasc Intervent Radiol 21:208–213CrossRefGoogle Scholar
  22. 22.
    Chiras J, Adem C, Vallee JN, Spelle L, Cormier E, Rose M (2004) Selective intra-arterial chemoembolization of pelvic and spine bone metastases. Eur Radiol 13:1774–1780Google Scholar
  23. 23.
    Koike Y, Takizawa K, Ogawa Y et al (2011) Transcatheter arterial chemoembolization (TACE) or embolization (TAE) for symptomatic bone metastases as a palliative treatment. Cardiovasc Intervent Radiol 34:793–801CrossRefGoogle Scholar
  24. 24.
    Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540CrossRefGoogle Scholar
  25. 25.
    Diamond E, Molina AM, Carbonaro M et al (2015) Cytotoxic chemotherapy in the treatment of advanced renal cell carcinoma in the era of targeted therapy. Crit Rev Oncol Hematol 96:518–526CrossRefGoogle Scholar
  26. 26.
    Hussain M, Vaishampayan U, Du W, Redman B, Smith DC (2001) Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer. J Clin Oncol 19:2527–2533CrossRefGoogle Scholar
  27. 27.
    Hosogoe S, Hatakeyama S, Kusaka A et al (2018) Platinum-based neoadjuvant chemotherapy improves oncological outcomes in patients with locally advanced upper tract urothelial carcinoma. Eur Urol Focus 4:946–953CrossRefGoogle Scholar
  28. 28.
    Drooz AT, Lewis CA, Allen TE et al (2003) Quality improvement guidelines for percutaneous transcatheter embolization. J Vasc Interv Radiol 14:S237–S242PubMedGoogle Scholar
  29. 29.
    Mizumoto M, Hrada H, Asakura H et al (2009) Radiotherapy for patients with metastases to the spinal column: a review of 603 patients at Shizuoka Cancer Center Hospital. Int J Radiat Oncol Biol Phys 79:208–213CrossRefGoogle Scholar
  30. 30.
    Soo CS, Wallace S, Chuang VP, Carrasco CH, Phillies G (1982) Lumbar artery embolization in cancer patients. Radiology 145:655–659CrossRefGoogle Scholar
  31. 31.
    Uemura A, Fujimoto H, Yasuda S et al (2001) Transcatheter arterial embolization for bone metastases from hepatocellular carcinoma. Eur Radiol 11:1457–1462CrossRefGoogle Scholar
  32. 32.
    Yamaura H, Yamada K, Matsuzawa T (1976) Radiation effect on the proliferating capillaries in rat transparent chambers. Int J Radiat Biol Relat Stud Phys Chem Med 30:179–187CrossRefGoogle Scholar
  33. 33.
    Yamaura H, Matsuzawa T (1979) Tumor regrowth after irradiation: an experimental approach. Int J Radiat Biol Relat Stud Phys Chem Med 35:201–219CrossRefGoogle Scholar
  34. 34.
    Coldwell DM, Stokes KR, Yakes WF (1994) Embolotherapy: agents, clinical applications and techniques. Radiographics 14:623–643CrossRefGoogle Scholar
  35. 35.
    Kato T, Nemoto R, Mori H, Takahashi M, Harada M (1981) Arterial chemoembolization with mitomycin C microcapsules in the treatment of primary or secondary carcinoma of the kidney, liver bone and intrapelvic organs. Cancer 48:674–680CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Joichi Heianna
    • 1
    Email author
  • Wataru Makino
    • 1
  • Takuro Ariga
    • 1
  • Kazuki Ishikawa
    • 1
  • Takeaki Kusada
    • 1
  • Hitoshi Maemoto
    • 1
  • Masafumi Toguchi
    • 1
  • Junji Ito
    • 1
  • Masato Goya
    • 2
  • Minoru Miyazato
    • 2
  • Yuko Iraha
    • 1
  • Sadayuki Murayama
    • 1
  1. 1.Department of RadiologyGraduate School of Medical Science University of The RyukyusNishiharaJapan
  2. 2.Department of UrologyGraduate School of Medical Science University of The RyukyusNishiharaJapan

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