Treatment of Bone Metastases: Future Directions

  • Guido ScocciantiEmail author
  • Rodolfo Capanna


Four main future directions in the treatment of bone metastases can likely be envisaged: fewer tumors in general population, fewer bone metastases in patients affected by tumors, less invasive therapies, and in selected cases highly invasive surgery also in metastatic patients who have been often banished to palliative treatment so far. Development and improvements of current techniques and introduction of new technological achievements are expected to improve actual therapeutic regimens. Nanotechnologies and a combination of diagnosis and treatment in the same time (theranostics) are likely to deeply change our approach to bone metastatic disease and, we hope, its results. New and less invasive surgical procedures are going to progressively decrease the surgical burden on most of the metastatic patients who will still need surgery, but at the same time, a growing number of these patients will undergo highly invasive surgery, due to the application of the criteria of primary tumor surgery also to metastatic patients, thanks to the improved survival. The future of the treatment of bone metastases will surely be a varied and variegated future, ranging from the use of extremely small devices, like nanoprobes, to the use of megaprostheses, and maybe also combinations of them. The clinician will have to be ready to manage a continuously growing range of therapeutic options and to have the capability to choose the right one for the specific patient.


Bone metastases Orthopedic oncology Mini-invasive surgery Nanomedicine Future treatments 


  1. 1.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.CrossRefGoogle Scholar
  2. 2.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.CrossRefGoogle Scholar
  3. 3.
    Lim EK, Kim T, Paik S, Haam S, Huh YM, Lee K. Nanomaterials for theranostics: recent advances and future challenges. Chem Rev. 2015;115:327–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW, et al. Cancer genome landscapes. Science. 2013;339:1546–58.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Iyer AK, Khaled G, Fang J, Maeda H. Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today. 2006;11:812–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Hirsjärvi S, Passirani C, Benoit JP. Passive and active tumor targeting with nanocarriers. Curr Drug Discov Technol. 2011;8:188–96.CrossRefPubMedGoogle Scholar
  7. 7.
    Bonzi G, Salmaso S, Scomparin A, Eldar-Boock A, Satch-Fainaro R, Caliceti P. Novel pullulan bioconjugate for selective breast cancer bone metastases treatment. Bioconjug Chem. 2015;26:489–501.CrossRefPubMedGoogle Scholar
  8. 8.
    Chen H, Li G, Chi H, Wang D, Tu C, Pan L, Zhu L, Qiu F, Guo F, Zhu X. Alendronate-conjugated amphiphilic hyperbranched polymer based on Boltorn H40 and poly(ethylene glycol) for bone-targeted drug delivery. Bioconjug Chem. 2012;23:1915–24.CrossRefPubMedGoogle Scholar
  9. 9.
    Miller K, Erez R, Segal E, Shabat D, Satchi-Fainaro R. Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate. Angew Chem. 2009;48:2949–54.CrossRefGoogle Scholar
  10. 10.
    Pignatello R, Sarpietro MG, Castelli F. Synthesis and biological evaluation of a new polymeric conjugate and nanocarrier with osteotropic properties. J Funct Biomater. 2012;3:79–99.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Krishnan S, Diagaradjane P, Cho S. Nanoparticle-mediated thermal therapy: evolving strategies for prostate cancer therapy. Int J Hyperth. 2010;26:775–89.CrossRefGoogle Scholar
  12. 12.
    Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011;103:317–24.CrossRefGoogle Scholar
  13. 13.
    Agarwal A, Mackey MA, El-Sayed MA, Bellamkonda RV. Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods. ACS Nano. 2011;5:4919–26.CrossRefPubMedGoogle Scholar
  14. 14.
    Park JH, von Maltzahn G, Ong LL, Centrone A, Hatton TA, Ruoslahti E, et al. Cooperative nanoparticles for tumor detection and photothermally triggered drug delivery. Adv Mater. 2010;22:880–5.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Green B, Cobb ARM, Hopper C. Photodynamic therapy in the management of lesions of the head and neck. Br J Oral Maxillofac Surg. 2013;51:283–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Nahashima A, Nagayasu T. Current status of photodynamic therapy in digestive tract carcinoma in Japan. Int J Mol Sci. 2015;16:3430–40.Google Scholar
  17. 17.
    Simone CB, Cengel KA. Photodynamic therapy for lung cancer and malignant pleural mesothelioma. Semin Oncol. 2014;41:820–30.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yano T, Muto M, Yoshimura K, Niimi M, Ezoe Y, Yoda Y, et al. Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherpay for esophageal cancer. Radiat Oncol. 2012;7:113.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dagan R, Lo SS, Redmond KJ, Poon I, Foote MC, Lohr F, et al. A multi-national report on stereotactic body radiotherapy for oligometastases: patient selection and follow-up. Acta Oncol. 2016;55:633–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Tree AC, Khoo VS, Eeles RA, Ahmed M, Dearnaley DP, Hawkins MA, et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol. 2013;14:e28–37.CrossRefPubMedGoogle Scholar
  21. 21.
    Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13:8–10.CrossRefPubMedGoogle Scholar
  22. 22.
    El-Amm J, Aragon-Ching JB. Targeting bone metastases in metastatic castration-resistant prostate cancer. Clin Med Insights Oncol. 2016;10:11–9.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kairemo K, Joensuu T. Radium-223-dichloride in castration resistant metastatic prostate cancer-preliminary results of the response evaluation using F-18-fluoride PET/CT. Diagnostics. 2015;5:413–27.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.CrossRefPubMedGoogle Scholar
  25. 25.
    Yuan J, Liu C, Liu X, Wang Y, Kuai D, Zhang G, et al. Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study. Clin Nucl Med. 2013;38:88–92.CrossRefPubMedGoogle Scholar
  26. 26.
    Song L, Falzone N, Vallis KA. EGF-coated gold nanoparticles provide an efficient nano-scale delivery system for the molecular radiotherapy of EGFR-positive cancer. Int J Radiat Biol. 2016;21:1–8.Google Scholar
  27. 27.
    Miklavčič D, Serša G, Brecelj E, Gehl J, Soden D, Bianchi G, et al. Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors. Med Biol Eng Comput. 2012;50:1213–25.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Callstrom MR, Dupuy DE, Solomon SB, Beres RA, Littrup PJ, Davis KW, et al. Percutaneous image-guided cryoablation of painful metastases involving bone: multicenter trial. Cancer. 2013;119:1033–41.CrossRefPubMedGoogle Scholar
  29. 29.
    Damian E, Dupuy DE, Liu D, Hartfeil D, Hanna L, Blume JD, et al. Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial. Cancer. 2010;116:989–97.CrossRefGoogle Scholar
  30. 30.
    Deschamps F, Farouil G, Ternes N, Gaudin A, Hakime A, Tselikas L, et al. Thermal ablation techniques: a curative treatment of bone metastases in selected patients? Eur Radiol. 2014;24:1971–80.CrossRefPubMedGoogle Scholar
  31. 31.
    Goetz MP, Callstrom MR, Charboneau JW, Farrell MA, Maus TP, Welch TJ, et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol. 2004;22:300–6.CrossRefPubMedGoogle Scholar
  32. 32.
    McMenomy BP, Kurup AN, Johnson GB, Carter RE, McWilliams RR, Markovic SN, et al. Percutaneous cryoablation of musculoskeletal oligometastatic disease for complete remission. J Vasc Interv Radiol. 2013;24:207–13.CrossRefPubMedGoogle Scholar
  33. 33.
    Thacker PG, Callstrom MR, Curry TB, Mandrekar JN, Atwell TD, Goetz MP, et al. Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients’ immediate response to radiofrequency ablation and cryoablation. AJR Am J Roentgenol. 2011;197:510–5.CrossRefPubMedGoogle Scholar
  34. 34.
    Thanos L, Mylona S, Galani P, Tzavoulis D, Kalioras V, Tanteles S, et al. Radiofrequency ablation of osseous metastases for the palliation of pain. Skelet Radiol. 2008;37:189–94.CrossRefGoogle Scholar
  35. 35.
    Kurup AN, Callstrom MR. Ablation of musculoskeletal metastases: pain palliation, fracture risk reduction, and oligometastatic disease. Tech Vasc Interv Radiol. 2013;16:253–61.CrossRefPubMedGoogle Scholar
  36. 36.
    Callstrom MR, Kurup AN. Percutaneous ablation for bone and soft tissue metastases—why cryoablation? Skelet Radiol. 2009;38:835–9.CrossRefGoogle Scholar
  37. 37.
    Liberman B, Gianfelice D, Inbar Y, Beck A, Rabin T, Shabshin N, et al. Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study. Ann Surg Oncol. 2009;16:140–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Tempany CM, McDannold NJ, Hynynen K, Jolesz FA. Focused ultrasound surgery in oncology: overview and principles. Radiology. 2011;259:39–56.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lo VC, Akens MK, Moore S, Yee AJ, Wilson BC, Whyne CM. Beyond radiation therapy: photodynamic therapy maintains structural integrity of irradiated healthy and metastatically involved vertebrae in a pre-clinical in vivo model. Breast Cancer Res Treat. 2012;135:391–401.CrossRefPubMedGoogle Scholar
  40. 40.
    Zimel MN, Hwang S, Riedel ER, Healey JH. Carbon fiber intramedullary nails reduce artifact in postoperative advanced imaging. Skelet Radiol. 2015;44:1317–25.CrossRefGoogle Scholar
  41. 41.
    Vegt P, Muir JM, Block JE. The photodynamic bone stabilization system: a minimally invasive, percutaneous intramedullary polymeric osteosynthesis for simple and complex long bone fractures. Med Devices (Auckl). 2014;7:453–61.Google Scholar
  42. 42.
    Hadjipanayis CG, Widhalm G, Stummer W. What is the surgical benefit of utilizing 5-aminolevulinic acid for fluorescence-guided surgery of malignant gliomas? Neurosurgery. 2015;77:663–73.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392–401.CrossRefPubMedGoogle Scholar
  44. 44.
    Zhao S, Wu J, Wang C, Liu H, Dong X, Shi C, et al. Intraoperative fluorescence-guided resection of high-grade malignant gliomas using 5-aminolevulinic acid-induced porphyrins: a systematic review and meta-analysis of prospective studies. PLoS One. 2013;8:e63682.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    McElroy M, Kaushal S, Luiken GA, Talamini MA, Moossa AR, Hoffman RM, et al. Imaging of primary and metastatic pancreatic cancer using a fluorophore conjugated anti-CA19-9 antibody for surgical navigation. World J Surg. 2008;32:1057.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Van Dam GM, Themelis G, Crane LM, Harlaar NJ, Pleijhuis RG, Kelder W, et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med. 2011;17:1315–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Miwa S, Matsumoto Y, Hiroshima Y, Yano S, Uehara F, Yamamoto M, et al. Fluorescence-guided surgery of prostate cancer bone metastasis. J Surg Res. 2014;192:124–33.CrossRefPubMedGoogle Scholar
  48. 48.
    Miwa S, De Magalhães N, Toneri M, Zhang Y, Cao W, Bouvet M, et al. Fluorescence-guided surgery of human prostate cancer experimental bone metastasis in nude mice using anti-CEA DyLight 650 for tumor illumination. J Orthop Res. 2016;34:559–65.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Orthopaedic Oncology and Reconstructive SurgeryCareggi University HospitalFlorenceItaly
  2. 2.Department of Orthopaedics and Traumatology, Translational Research and Innovative TechniquesUniversity of PisaPisaItaly

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