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Prognostic significance of intensive local therapy to bone lesions in renal cell carcinoma patients with bone metastasis

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Abstract

We evaluated the prognostic roles of local therapy to bone metastasis (BM) in metastatic renal cell carcinoma (mRCC) patients with BM. This retrospective study included 71 mRCC patients with BM. Local therapy to BM included en bloc resection, curettage, and radiotherapy (RT). RT was classified into RT with biological effective dose (BED) ≥85 Gy and <85 Gy by its therapeutic intensity. Local therapy to BM was given for 64 patients (90 %): en bloc resection, curettage, and RT for 16, 10, and 38 patients, respectively. Fifteen patients received RT with BED ≥85 Gy. The median overall survival (OS) was 25 months (median follow-up 16 months). For 46 patients with solitary BM, patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy showed significantly better OS than those treated with RT with BED <85 Gy or no local therapy (P = 0.006). Because OS was comparable among patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy, these three treatment modalities were defined as “intensive local therapy”. Intensive local therapy to BM was also associated with favorable OS with marginal significance (P = 0.052) in a cohort of 25 patients with multiple BM. A multivariate analysis in the whole cohort revealed that intensive local therapy to BM was independently associated with favorable OS (hazard ratio 0.23, P < 0.001) along with Memorial-Sloan Kettering Cancer Center risk category (P < 0.001). Thus, intensive local therapy to BM might improve OS in mRCC patients with BM including multiple BM.

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Abbreviations

ALP:

Alkaline phosphatase

BED:

Biological effective dose

BM:

Bone metastasis

CRP:

C-reactive protein

EBRT:

External beam radiotherapy

IORT:

Intraoperative radiotherapy

mRCC:

Metastatic renal cell carcinoma

MSKCC:

Memorial-Sloan Kettering Cancer Center

OS:

Overall survival

PS:

Performance status

RCC:

Renal cell carcinoma

RT:

Radiotherapy

SBRT:

Stereotactic body radiotherapy

SRE:

Skeletal-related event

References

  1. Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA (2011) The epidemiology of renal cell carcinoma. Eur Urol 60(4):615–621. doi:10.1016/j.eururo.2011.06.049

    Article  PubMed  Google Scholar 

  2. Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335(12):865–875. doi:10.1056/NEJM199609193351207

    Article  CAS  PubMed  Google Scholar 

  3. Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P, Menon M, Montorsi F, Karakiewicz PI (2012) Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 23(4):973–980. doi:10.1093/annonc/mdr362

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. 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 

  6. 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 

  7. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116(18):4256–4265. doi:10.1002/cncr.25219

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Riechelmann RP, Chin S, Wang L, Tannock IF, Berthold DR, Moore MJ, Knox JJ (2008) Sorafenib for metastatic renal cancer: the Princess Margaret experience. Am J Clin Oncol 31(2):182–187. doi:10.1097/COC.0b013e3181574084

    Article  CAS  PubMed  Google Scholar 

  10. Zekri J, Ahmed N, Coleman RE, Hancock BW (2001) The skeletal metastatic complications of renal cell carcinoma. Int J Oncol 19(2):379–382

    CAS  PubMed  Google Scholar 

  11. Jhaveri PM, Teh BS, Paulino AC, Blanco AI, Lo SS, Butler EB, Amato RJ (2012) A dose-response relationship for time to bone pain resolution after stereotactic body radiotherapy (SBRT) for renal cell carcinoma (RCC) bony metastases. Acta Oncol 51(5):584–588. doi:10.3109/0284186X.2011.652741

    Article  PubMed  Google Scholar 

  12. Wilson D, Hiller L, Gray L, Grainger M, Stirling A, James N (2003) The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma. Clin Oncol 15(7):400–407

    Article  CAS  Google Scholar 

  13. Lin PP, Mirza AN, Lewis VO, Cannon CP, Tu SM, Tannir NM, Yasko AW (2007) Patient survival after surgery for osseous metastases from renal cell carcinoma. J Bone Joint Surg Am 89(8):1794–1801. doi:10.2106/JBJS.F.00603

    Article  PubMed  Google Scholar 

  14. Fuchs B, Trousdale RT, Rock MG (2005) Solitary bony metastasis from renal cell carcinoma: significance of surgical treatment. Clin Orthop Relat Res 431:187–192

    Article  PubMed  Google Scholar 

  15. Saito K, Tatokoro M, Fujii Y, Iimura Y, Koga F, Kawakami S, Kihara K (2009) Impact of C-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma. Eur Urol 55(5):1145–1153. doi:10.1016/j.eururo.2008.10.012

    Article  CAS  PubMed  Google Scholar 

  16. Motzer RJ, Bukowski RM, Figlin RA, Hutson TE, Michaelson MD, Kim ST, Baum CM, Kattan MW (2008) Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer 113(7):1552–1558. doi:10.1002/cncr.23776

    Article  CAS  PubMed  Google Scholar 

  17. Vogl UM, Zehetgruber H, Dominkus M, Hejna M, Zielinski CC, Haitel A, Schmidinger M (2006) Prognostic factors in metastatic renal cell carcinoma: metastasectomy as independent prognostic variable. Br J Cancer 95(6):691–698. doi:10.1038/sj.bjc.6603327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Soltan M, Smiler D, Choi JH (2009) Bone marrow: orchestrated cells, cytokines, and growth factors for bone regeneration. Implant Dent 18(2):132–141. doi:10.1097/ID.0b013e3181990e75

    Article  PubMed  Google Scholar 

  19. Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350(16):1655–1664. doi:10.1056/NEJMra030831

    Article  CAS  PubMed  Google Scholar 

  20. Castellano D, Sepulveda JM, Garcia-Escobar I, Rodriguez-Antolin A, Sundlov A, Cortes-Funes H (2011) The role of RANK-ligand inhibition in cancer: the story of denosumab. Oncologist 16(2):136–145. doi:10.1634/theoncologist.2010-0154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors acknowledge Prof. Kazunori Kihara and Prof. Yasuhisa Fujii (Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan) for their thoughtful advice and encouragement throughout the present study. The authors declare that there is no fund of research, grants and financial support.

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Correspondence to Fumitaka Koga.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Fukushima, H., Hozumi, T., Goto, T. et al. Prognostic significance of intensive local therapy to bone lesions in renal cell carcinoma patients with bone metastasis. Clin Exp Metastasis 33, 699–705 (2016). https://doi.org/10.1007/s10585-016-9805-y

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