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The fat body mass increase after adjuvant androgen deprivation therapy is predictive of prostate cancer outcome

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Abstract

Androgen deprivation therapy (ADT) leads to important changes in body composition. No data are currently available about the relationship between these treatment-related changes and patient outcome. Using dual-energy X-ray absorptiometry, bone mineral density (BMD), fat body mass (FBM), and lean body mass (LBM) were determined at baseline, and after 1 and 2 years in 53 non-metastatic prostate cancer (PC) patients with high-risk disease treated with adjuvant ADT. Changes in these parameters were correlated with patient outcome in terms of adverse skeletal events, disease recurrence, and overall survival. ADT led to a significant decrease in BMD (p < 0.03) and LBM (p < 0.03), and an increase in FBM, (p < 0.0001). Changes in BMD failed to show any relationship with time to skeletal-related events (SRE), disease recurrence, and death. FBM increase was a significant predictor of higher risk of SRE [hazard ratio (HR) 3.024, 95 % CI 1.004–10.353, p < 0.02], higher risk of death (HR 2.373, 95 % CI 1.012–5.567, p = 0.04), and a non-significant higher risk of disease recurrence (HR 2.219, 95 % CI 0.956–5.150, p = 0.13). LBM decrease did not correlate with either time to SRE or survival, while a non-significant association with disease recurrence (HR 1.550, 95 % CI 0.670–3.605, p = 0.06) was observed. The early increase in FBM may provide predictive information of poor outcome in PC patients given ADT. These data suggest that the adoption of early preventive measures aiming to reduce fat increase can potentially reduce the morbidity and mortality risk.

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References

  1. P. Hammerer, S. Madersbacher, Landmarks in hormonal therapy for prostate cancer. BJU Int. 110(Suppl 1), 23–29 (2012)

    Article  CAS  PubMed  Google Scholar 

  2. F. Haseen, L.J. Murray, C.R. Cardwell, J.M. O’Sullivan, M.M. Cantwell, The effect of androgen deprivation therapy on body composition in men with prostate cancer: systematic review and meta-analysis. J. Cancer Surviv. 4(2), 128–139 (2010)

    Article  PubMed  Google Scholar 

  3. S.J. Freedland, W.J. Aronson, C.J. Kane, J.C. Presti Jr, C.L. Amling, D. Elashoff, M.K. Terris, Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the Shared Equal Access Regional Cancer Hospital database study group. J. Clin. Oncol. 22(3), 446–453 (2004)

    Article  PubMed  Google Scholar 

  4. C.L. Amling, R.H. Riffenburgh, L. Sun, J.W. Moul, R.S. Lance, L. Kusuda, W.J. Sexton, D.W. Soderdahl, T.F. Donahue, J.P. Foley, A.K. Chung, D.G. McLeod, Pathologic variables and recurrence rates as related to obesity and race in men with prostate cancer undergoing radical prostatectomy. J. Clin. Oncol. 22(3), 439–445 (2004)

    Article  PubMed  Google Scholar 

  5. J.C. Keto, W.J. Aronson, M.K. Terris, J.C. Presti, C.J. Kane, C.L. Amling, S.J. Freedland, Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database. BJU Int. 110(4), 492 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. J. Ma, H. Li, E. Giovannucci, L. Mucci, W. Qiu, P.L. Nguyen, J.M. Gaziano, M. Pollak, M.J. Stampfer, Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis. Lancet Oncol. 9(11), 1039–1047 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. M.R. Smith, K. Bae, J.A. Efstathiou, G.E. Hanks, M.V. Pilepich, H.M. Sandler, W.U. Shipley, Diabetes and mortality in men with locally advanced prostate cancer: RTOG 92-02. J. Clin. Oncol. 10(26), 4333–4339 (2008)

    Article  Google Scholar 

  8. E. Andrès, P. Eschwege, H. Lang, J.L. Moreau, D. Peiffert, A. Thiery-Vuillemin, F. Kleinclauss, Metabolic impact of androgen deprivation therapy for prostate cancer. Prog. Urol. 22(Suppl 2), S39–S47 (2012)

    Article  PubMed  Google Scholar 

  9. M. Grossmann, G. Wittert, Androgens, diabetes and prostate cancer. Endocr. Relat. Cancer 19(5), F47–F62 (2012)

    Article  CAS  PubMed  Google Scholar 

  10. P.J. Saylor, K.R. Kozak, M.R. Smith, M.A. Ancukiewicz, J.A. Efstathiou, A.L. Zietman, R.K. Jain, D.G. Duda, Changes in biomarkers of inflammation and angiogenesis during androgen deprivation therapy for prostate cancer. Oncologist 17(2), 212 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. A. Berruti, L. Dogliotti, C. Terrone, S. Cerutti, G. Isaia, R. Tarabuzzi, G. Reimondo, M. Mari, P. Ardissone, S. De Luca, G. Fasolis, D. Fontana, S.R. Rossetti, A. Angeli, Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy. J. Urol. 167(6), 2361–2367 (2002)

    Article  PubMed  Google Scholar 

  12. M.R. Smith, H. Lee, F. McGovern, M.A. Fallon, M. Goode, A.L. Zietman, J.S. Finkelstein, Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome. Cancer 112(10), 2188–2194 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. M.R. Smith, J.S. Finkelstein, F.J. McGovern, A.L. Zietman, M.A. Fallon, D.A. Schoenfeld, P.W. Kantoff, Changes in body composition during androgen deprivation therapy for prostate cancer. J. Clin. Endocrinol. Metab. 87(2), 599–603 (2002)

    Article  CAS  PubMed  Google Scholar 

  14. L.A. Nasto, A. Fusco, D. Colangelo, M. Mormando, G. Di Giacomo, B. Rossi, L. De Marinis, C.A. Logroscino, E. Pola, Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis. Eur. Rev. Med. Pharmacol. Sci. 16(9), 1227 (2012)

    CAS  PubMed  Google Scholar 

  15. T.D. Blackburn, D.B. Howard, E.S. Leib, Utility of spine bone mineral density in fracture prediction within FRAX. J. Clin. Densitom. 16(1), 81–86 (2013)

    Article  PubMed  Google Scholar 

  16. D. Scherr, P.W. Swindle, P.T. Scardino, National Comprehensive Cancer Network guidelines for the management of prostate cancer. Urology 61(2 Suppl 1), 14–24 (2003)

    Article  PubMed  Google Scholar 

  17. M. Braga-Basaria, A.S. Dobs, D.C. Muller, M.A. Carducci, M. John, J. Egan, S. Basaria, Metabolic syndrome in men with prostate cancer ongoing long-term androgen deprivation therapy. J. Clin. Oncol. 24, 3979–3983 (2006)

    Article  PubMed  Google Scholar 

  18. P. Hakimiam, M. Blute Jr, J. Kashanian, S. Chan, D. Silver, R. Shabsigh, Metabolic and cardiovascular effects of androgen deprivation therapy. BJUI 102, 1509–1514 (2008)

    Article  Google Scholar 

  19. M.R. Smith, H. Lee, M.A. Fallon, D.M. Nathan, Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer: evidence for a distinct hypogonadal metabolic syndrome? Urology 71(2), 318–322 (2008)

    Article  PubMed Central  PubMed  Google Scholar 

  20. W.C. Buschemeyer, S.J. Freedland, Obesity and prostate cancer: epidemiology and clinical implications. Eur. Urol. 52(2), 331–343 (2007)

    Article  PubMed  Google Scholar 

  21. J. Lessard, A. Tchernof, Interaction of the glucocorticoid and androgen receptors in adipogenesis. Chem. Biol. 19(9), 1079–1080 (2012)

    Article  CAS  PubMed  Google Scholar 

  22. K. Torimoto, S. Samma, Y. Kagebayashi, Y. Chihara, N. Tanaka, A. Hirayama, K. Fujimoto, Y. Hirao, The effects of androgen deprivation therapy on lipid metabolism and body composition in Japanese patients with prostate cancer. Jnp. J. Clin. Oncol. 41(4), 577–581 (2011)

    Article  Google Scholar 

  23. C. Ribot, F. Trémollières, J.M. Pouillès, The effect of obesity on postmenopausal bone loss and the risk of osteoporosis. Adv. Nutr. Res. 9, 257–271 (1994)

    CAS  PubMed  Google Scholar 

  24. S.M. Alibhai, L. Yun, A.M. Cheung, L. Paszat, Screening for osteoporosis in men receiving androgen deprivation therapy. JAMA 307(3), 255–256 (2012)

    Article  CAS  PubMed  Google Scholar 

  25. P.J. Snyder, H. Peachey, P. Hannoush, J.A. Berlin, L. Loh, D.A. Lenrow, J.H. Holmes, A. Dlewati, J. Santanna, C.J. Rosen, B.L. Strom, Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J. Clin. Endocrinol. Metab. 84(8), 2647–2653 (1999)

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Medical Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Italy

    Consuelo Buttigliero, Federica Vana, Valentina Bertaglia, Francesca Vignani, Marcello Tucci & Giorgio Vittorio Scagliotti

  2. Department of Urology, University of Turin at San Luigi Hospital, Orbassano, Italy

    Cristian Fiori & Francesco Porpiglia

  3. Department of Internal Medicine, University of Turin at San Luigi Hospital, Orbassano, Italy

    Giangiacomo Osella

  4. Medical Oncology, University of Brescia at Spedali Civili Hospital, Brescia, Italy

    Alfredo Berruti

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  1. Consuelo Buttigliero
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  2. Federica Vana
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  3. Valentina Bertaglia
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  4. Francesca Vignani
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Correspondence to Consuelo Buttigliero.

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Buttigliero, C., Vana, F., Bertaglia, V. et al. The fat body mass increase after adjuvant androgen deprivation therapy is predictive of prostate cancer outcome. Endocrine 50, 223–230 (2015). https://doi.org/10.1007/s12020-015-0525-x

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  • DOI: https://doi.org/10.1007/s12020-015-0525-x

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