Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2015

Open Access 01-12-2015 | Research

Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis?

Authors: Matteo Santoni, Alessandro Conti, Giuseppe Procopio, Camillo Porta, Toni Ibrahim, Sandro Barni, Francesco Maria Guida, Andrea Fontana, Alfredo Berruti, Rossana Berardi, Francesco Massari, Bruno Vincenzi, Cinzia Ortega, Davide Ottaviani, Giacomo Carteni, Gaetano Lanzetta, Delia De Lisi, Nicola Silvestris, Maria Antonietta Satolli, Elena Collovà, Antonio Russo, Giuseppe Badalamenti, Stefano Luzi Fedeli, Francesca Maria Tanca, Vincenzo Adamo, Evaristo Maiello, Roberto Sabbatini, Alessandra Felici, Saverio Cinieri, Rodolfo Montironi, Sergio Bracarda, Giuseppe Tonini, Stefano Cascinu, Daniele Santini

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2015

Login to get access

Abstract

Purpose

Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC).

Materials and methods

Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: <1 year, between 1 and 5 years and >5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance.

Results

470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 − 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology (p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM <1 year (13 months) or between 1 and 5 years (19 months) from nephrectomy (p < 0.001), no difference was found between these two last groups (p = 0.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs.

Conclusions

Our study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.
Literature
1.
go back to reference Murai M, Oya M. Renal cell carcinoma: etiology, incidence and epidemiology. Curr Opin Urol. 2004;14:229–33.CrossRefPubMed Murai M, Oya M. Renal cell carcinoma: etiology, incidence and epidemiology. Curr Opin Urol. 2004;14:229–33.CrossRefPubMed
2.
go back to reference Athar U, Gentile TC. Treatment options for metastatic renal cell carcinoma: a review. Can J Urol. 2008;15:3954–66.PubMed Athar U, Gentile TC. Treatment options for metastatic renal cell carcinoma: a review. Can J Urol. 2008;15:3954–66.PubMed
4.
go back to reference Woodward E, Jagdev S, McParland L, Clark K, Gregory W, Newsham A, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48:160–6.CrossRefPubMed Woodward E, Jagdev S, McParland L, Clark K, Gregory W, Newsham A, et al. Skeletal complications and survival in renal cancer patients with bone metastases. Bone. 2011;48:160–6.CrossRefPubMed
6.
go back to reference Facchini G, Caraglia M, Santini D, Nasti G, Ottaiano A, Striano S, et al. The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE). J Exp Clin Cancer Res. 2007;26:307–12.PubMed Facchini G, Caraglia M, Santini D, Nasti G, Ottaiano A, Striano S, et al. The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE). J Exp Clin Cancer Res. 2007;26:307–12.PubMed
7.
go back to reference Santini D, Procopio G, Porta C, Ibrahim T, Barni S, Mazzara C, et al. Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey. PLoS One. 2013;8:e83026.CrossRefPubMedCentralPubMed Santini D, Procopio G, Porta C, Ibrahim T, Barni S, Mazzara C, et al. Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey. PLoS One. 2013;8:e83026.CrossRefPubMedCentralPubMed
8.
go back to reference Beuselinck B, Oudard S, Rixe O, Wolter P, Blesius A, Ayllon J, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22:794–800.CrossRefPubMed Beuselinck B, Oudard S, Rixe O, Wolter P, Blesius A, Ayllon J, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22:794–800.CrossRefPubMed
9.
go back to reference Choueiri TK, Garcia JA, Elson P, Khasawneh M, Usman S, Golshayan AR, et al. Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer. 2007;110:543–50.CrossRefPubMed Choueiri TK, Garcia JA, Elson P, Khasawneh M, Usman S, Golshayan AR, et al. Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer. 2007;110:543–50.CrossRefPubMed
10.
go back to reference Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.CrossRefPubMed Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.CrossRefPubMed
11.
go back to reference Santoni M, Santini D, Massari F, Conti A, Iacovelli R, Burattini L, et al. Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside. Cancer Metastasis Rev. 2014;33:321–31.CrossRefPubMed Santoni M, Santini D, Massari F, Conti A, Iacovelli R, Burattini L, et al. Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside. Cancer Metastasis Rev. 2014;33:321–31.CrossRefPubMed
12.
go back to reference Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med. 1998;17:873–90.CrossRefPubMed Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med. 1998;17:873–90.CrossRefPubMed
13.
go back to reference Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol. 2004;22:454–63.CrossRefPubMed Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol. 2004;22:454–63.CrossRefPubMed
14.
go back to reference Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. 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. 2009;27:5794–9.CrossRefPubMed Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. 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. 2009;27:5794–9.CrossRefPubMed
15.
go back to reference Kroeger N, Choueiri TK, Lee JL, Bjarnason GA, Knox JJ, MacKenzie MJ, et al. Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy. Eur Urol. 2014;65:1086–92.CrossRefPubMed Kroeger N, Choueiri TK, Lee JL, Bjarnason GA, Knox JJ, MacKenzie MJ, et al. Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy. Eur Urol. 2014;65:1086–92.CrossRefPubMed
16.
go back to reference Santoni M, Conti A, Porta C, Procopio G, Sternberg CN, Basso U, et al. Sunitinib, Pazopanib or Sorafenib for the Treatment of Patients with Late Relapsing Metastatic Renal Cell Carcinoma. J Urol. 2015;193:41–7. doi:10.1016/j.juro.2014.07.011.CrossRefPubMed Santoni M, Conti A, Porta C, Procopio G, Sternberg CN, Basso U, et al. Sunitinib, Pazopanib or Sorafenib for the Treatment of Patients with Late Relapsing Metastatic Renal Cell Carcinoma. J Urol. 2015;193:41–7. doi:10.1016/j.juro.2014.07.011.CrossRefPubMed
17.
go back to reference Hosmer WJ, Lemeshow S. Applied Survival Analysis: Regression Modeling of Time to Event Data. New York: John Wiley; 1999. Hosmer WJ, Lemeshow S. Applied Survival Analysis: Regression Modeling of Time to Event Data. New York: John Wiley; 1999.
18.
go back to reference Fizazi K, Yang J, Peleg S, Sikes CR, Kreimann EL, Daliani D, et al. Prostate cancer cells-osteoblast interaction shifts expression of growth/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts. Clin Cancer Res. 2003;9:2587–97.PubMed Fizazi K, Yang J, Peleg S, Sikes CR, Kreimann EL, Daliani D, et al. Prostate cancer cells-osteoblast interaction shifts expression of growth/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts. Clin Cancer Res. 2003;9:2587–97.PubMed
19.
go back to reference Shiirevnyamba A, Takahashi T, Shan H, Ogawa H, Yano S, Kanayama H, et al. Enhancement of osteoclastogenic activity in osteolytic prostate cancer cells by physical contact with osteoblasts. Br J Cancer. 2011;104:505–13.CrossRefPubMedCentralPubMed Shiirevnyamba A, Takahashi T, Shan H, Ogawa H, Yano S, Kanayama H, et al. Enhancement of osteoclastogenic activity in osteolytic prostate cancer cells by physical contact with osteoblasts. Br J Cancer. 2011;104:505–13.CrossRefPubMedCentralPubMed
20.
go back to reference Chen Y, Liu H, Wu W, Li Y, Li J. Osteopontin genetic variants are associated with overall survival in advanced non-small-cell lung cancer patients and bone metastasis. J Exp Clin Cancer Res. 2013;32:45.CrossRefPubMedCentralPubMed Chen Y, Liu H, Wu W, Li Y, Li J. Osteopontin genetic variants are associated with overall survival in advanced non-small-cell lung cancer patients and bone metastasis. J Exp Clin Cancer Res. 2013;32:45.CrossRefPubMedCentralPubMed
21.
go back to reference Chirgwin JM, Guise TA. Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr. 2000;10:159–78.CrossRefPubMed Chirgwin JM, Guise TA. Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr. 2000;10:159–78.CrossRefPubMed
22.
go back to reference Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2:584–93.CrossRefPubMed Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2:584–93.CrossRefPubMed
24.
go back to reference Joeckel E, Haber T, Prawitt D, Junker K, Hampel C, Thüroff JW, et al. High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor. Mol Cancer. 2014;13:42.CrossRefPubMedCentralPubMed Joeckel E, Haber T, Prawitt D, Junker K, Hampel C, Thüroff JW, et al. High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor. Mol Cancer. 2014;13:42.CrossRefPubMedCentralPubMed
25.
go back to reference Yang L, You S, Kumar V, Zhang C, Cao Y. In vitro the behaviors of metastasis with suppression of VEGF in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line. J Exp Clin Cancer Res. 2012;31:40.CrossRefPubMedCentralPubMed Yang L, You S, Kumar V, Zhang C, Cao Y. In vitro the behaviors of metastasis with suppression of VEGF in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line. J Exp Clin Cancer Res. 2012;31:40.CrossRefPubMedCentralPubMed
26.
go back to reference McKay RR, Lin X, Perkins JJ, Heng DY, Simantov R. Choueiri. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma Eur Urol. 2014;66:502–9. McKay RR, Lin X, Perkins JJ, Heng DY, Simantov R. Choueiri. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma Eur Urol. 2014;66:502–9.
27.
go back to reference Riechelmann RP, Chin S, Wang L, Tannock IF, Berthold DR, Moore MJ, et al. Sorafenib for metastatic renal cancer: the Princess Margaret experience. Am J Clin Oncol. 2008;31:182–7.CrossRefPubMed Riechelmann RP, Chin S, Wang L, Tannock IF, Berthold DR, Moore MJ, et al. Sorafenib for metastatic renal cancer: the Princess Margaret experience. Am J Clin Oncol. 2008;31:182–7.CrossRefPubMed
28.
go back to reference Lipton A, Colombo-Berra A, Bukowski RM, Rosen L, Zheng M, Urbanowitz G, et al. Skeletal complications in patients with bone metastases from renal cell carcinoma and therapeutic benefits of zoledronic acid. Clin Cancer Res. 2004;10:6397S–403.CrossRefPubMed Lipton A, Colombo-Berra A, Bukowski RM, Rosen L, Zheng M, Urbanowitz G, et al. Skeletal complications in patients with bone metastases from renal cell carcinoma and therapeutic benefits of zoledronic acid. Clin Cancer Res. 2004;10:6397S–403.CrossRefPubMed
29.
go back to reference Keizman D, Ish-Shalom M, Pili R, Hammers H, Eisenberger MA, Sinibaldi V, et al. 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. 2012;48:1031–7.CrossRefPubMed Keizman D, Ish-Shalom M, Pili R, Hammers H, Eisenberger MA, Sinibaldi V, et al. 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. 2012;48:1031–7.CrossRefPubMed
Metadata
Title
Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis?
Authors
Matteo Santoni
Alessandro Conti
Giuseppe Procopio
Camillo Porta
Toni Ibrahim
Sandro Barni
Francesco Maria Guida
Andrea Fontana
Alfredo Berruti
Rossana Berardi
Francesco Massari
Bruno Vincenzi
Cinzia Ortega
Davide Ottaviani
Giacomo Carteni
Gaetano Lanzetta
Delia De Lisi
Nicola Silvestris
Maria Antonietta Satolli
Elena Collovà
Antonio Russo
Giuseppe Badalamenti
Stefano Luzi Fedeli
Francesca Maria Tanca
Vincenzo Adamo
Evaristo Maiello
Roberto Sabbatini
Alessandra Felici
Saverio Cinieri
Rodolfo Montironi
Sergio Bracarda
Giuseppe Tonini
Stefano Cascinu
Daniele Santini
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2015
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-015-0122-0

Other articles of this Issue 1/2015

Journal of Experimental & Clinical Cancer Research 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine