Tumor Biology

, Volume 31, Issue 2, pp 97–102 | Cite as

Serum micronutrient and antioxidant levels at baseline and the natural history of men with localised prostate cancer on active surveillance

  • Ramachandran Venkitaraman
  • Karen Thomas
  • Phillip Grace
  • David P. Dearnaley
  • Alan Horwich
  • Robert A. Huddart
  • Christopher C. Parker
Research Article


The aim of this study was to determine whether serum concentrations of micronutrients, antioxidants and vitamins predict rate of disease progression in untreated, localised prostate cancer. Patients with localised prostatic adenocarcinoma on a prospective study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade ≥4 or >50% positive cores of total) or radical treatment for PSA velocity >1 ng ml−1 year−1. Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol, gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, retinol and selenium. One hundred four patients were evaluable, with a median follow-up of 2.5 years. Thirty-eight patients experienced disease progression, 13 biochemical and 25 histologic progression. Median time to disease progression was 2.62 years. No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol (p = 0.86), gamma-tocopherol (p = 0.84), alpha-carotenoid (p = 0.66), beta-carotene (p = 0.65), lycopene (p = 0.0.15), retinol (p = 0.76) or selenium (p = 0.76). No significant association was seen between serum levels of the micronutrients, antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity. Our data do not support the hypothesis that high serum concentrations of micronutrients, antioxidants and vitamins prevent disease progression in men with localised prostate cancer.


Prostate Active surveillance Antioxidants Micronutrients Vitamins 



This work was undertaken in The Royal Marsden NHS Trust which received a proportion of its funding from the NHS Executive; the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive. This work was supported by the Institute of Cancer Research, the Cancer Research UK Section of Radiotherapy (CRUK) grant no. C46/A2131 and the NCRI South of England Prostate Cancer Collaborative.


  1. 1.
    Elstner E, Campbell MJ, Munker R, Shintaku P, Binderup L, Heber D, et al. Novel 20-epi-vitamin D3 analog combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells. Prostate. 1999;40:141–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Quader ST, Bello-DeOcampo D, Williams DE, Kleinman HK, Webber MM. Evaluation of the chemopreventive potential of retinoids using a novel in vitro human prostate carcinogenesis model. Mutat Res. 2001;496:153–61.PubMedGoogle Scholar
  3. 3.
    Blumenfeld AJ, Fleshner N, Casselman B, Trachtenberg J. Nutritional aspects of prostate cancer: a review. Can J Urol. 2000;7:927–35. discussion 936.PubMedGoogle Scholar
  4. 4.
    Chang S, Erdman Jr JW, Clinton SK, Vadiveloo M, Strom SS, Yamamura Y, et al. Relationship between plasma carotenoids and prostate cancer. Nutr Cancer. 2005;53:127–34.CrossRefPubMedGoogle Scholar
  5. 5.
    Brett T. Prostate cancer. What part does diet play? Aust Fam Physician. 2000;29:1122–4.PubMedGoogle Scholar
  6. 6.
    Almushatat AS, Talwar D, McArdle PA, Williamson C, Sattar N, O'Reilly DS, et al. Vitamin antioxidants, lipid peroxidation and the systemic inflammatory response in patients with prostate cancer. Int J Cancer. 2006;118:1051–3.CrossRefPubMedGoogle Scholar
  7. 7.
    Duffield-Lillico AJ, Dalkin BL, Reid ME, Turnbull BW, Slate EH, Jacobs ET, et al. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int. 2003;91:608–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Kumar NB, Besterman-Dahan K. Nutrients in the chemoprevention of prostate cancer: current and future prospects. Cancer Control. 1999;6:580–6.PubMedGoogle Scholar
  9. 9.
    Weinstein SJ, Wright ME, Pietinen P, King I, Tan C, Taylor PR, et al. Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. J Natl Cancer Inst. 2005;97:396–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Clark LC, Dalkin B, Krongrad A, Combs Jr GF, Turnbull BW, Slate EH, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol. 1998;81:730–4.PubMedGoogle Scholar
  11. 11.
    Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev. 2001;10:861–8.PubMedGoogle Scholar
  12. 12.
    Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, et al. Effects of lycopene supplementation in patients with localized prostate cancer. Exp Biol Med (Maywood). 2002;227:881–5.Google Scholar
  13. 13.
    Ansari MS, Gupta NP. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int. 2003;92:375–8. discussion 378.CrossRefPubMedGoogle Scholar
  14. 14.
    Bowen PE. Selection of surrogate endpoint biomarkers to evaluate the efficacy of lycopene/tomatoes for the prevention/progression of prostate cancer. J Nutr. 2005;135:2068S–70S.PubMedGoogle Scholar
  15. 15.
    Huss WJ, Lai L, Barrios RJ, Hirschi KK, Greenberg NM. Retinoic acid slows progression and promotes apoptosis of spontaneous prostate cancer. Prostate. 2004;61:142–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Peehl DM, Feldman D. The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer. 2003;10:131–40.CrossRefPubMedGoogle Scholar
  17. 17.
    Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama. 2009;301:39–51.CrossRefPubMedGoogle Scholar
  18. 18.
    Klotz L. Active surveillance with selective delayed intervention for favorable risk prostate cancer. Urol Oncol. 2006;24:46–50.PubMedGoogle Scholar
  19. 19.
    Parker C. Active surveillance: towards a new paradigm in the management of early prostate cancer. Lancet Oncol. 2004;5:101–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Parker C. Active surveillance of early prostate cancer: rationale, initial results and future developments. Prostate Cancer Prostatic Dis. 2004;7:184–7.CrossRefPubMedGoogle Scholar
  21. 21.
    van den Bergh RC, Vasarainen H, van der Poel HG, Vis-Maters JJ, Rietbergen JB, Pickles T, et al. Short-term outcomes of the prospective multicentre ‘Prostate Cancer Research International: Active Surveillance’ study. BJU Int 2009 Oct 8.Google Scholar
  22. 22.
    Klotz LH. Active surveillance for good risk prostate cancer: rationale, method, and results. Can J Urol. 2005;12 Suppl 2:21–4.PubMedGoogle Scholar
  23. 23.
    Klotz L. Active surveillance with selective delayed intervention is the way to manage ‘good-risk’ prostate cancer. Nat Clin Pract Urol. 2005;2:136–42. quiz 131 p following 149.CrossRefPubMedGoogle Scholar
  24. 24.
    D'Amico AV, Renshaw AA, Sussman B, Chen MH. Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy. Jama. 2005;294:440–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Venkitaraman R, Norman A, Woode-Amissah R, Dearnaley D, Horwich A, Huddart R, et al. Prostate-specific antigen velocity in untreated, localized prostate cancer. BJU Int. 2008;101:161–4.PubMedGoogle Scholar
  26. 26.
    Venkitaraman R, Norman A, Woode-Amissah R, Fisher C, Dearnaley D, Horwich A, et al. Predictors of histological disease progression in untreated, localized prostate cancer. J Urol. 2007;178:833–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Jhavar S, Bartlett J, Kovacs G, Corbishley C, Dearnaley D, Eeles R, et al. Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance. Prostate Cancer Prostatic Dis. 2009;12:143–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res. 1999;59:1225–30.PubMedGoogle Scholar
  29. 29.
    Mohanty NK, Saxena S, Singh UP, Goyal NK, Arora RP. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urol Oncol. 2005;23:383–5.PubMedGoogle Scholar
  30. 30.
    Stacewicz-Sapuntzakis M, Bowen PE. Role of lycopene and tomato products in prostate health. Biochim Biophys Acta. 2005;1740:202–5.PubMedGoogle Scholar
  31. 31.
    Peters U, Littman AJ, Kristal AR, Patterson RE, Potter JD, White E. Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and Lifestyle (VITAL) Study cohort. Cancer Causes Control. 2008;19:75–87.CrossRefPubMedGoogle Scholar
  32. 32.
    Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2009;301:52–62.CrossRefPubMedGoogle Scholar
  33. 33.
    Allen NE, Appleby PN, Roddam AW, Tjonneland A, Johnsen NF, Overvad K, et al. Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Clin Nutr. 2008;88:1567–75.CrossRefPubMedGoogle Scholar
  34. 34.
    Schroder FH, Roobol MJ, Boeve ER, de Mutsert R, Zuijdgeest-van Leeuwen SD, Kersten I, et al. Randomized, double-blind, placebo-controlled crossover study in men with prostate cancer and rising PSA: effectiveness of a dietary supplement. Eur Urol. 2005;48:922–30. discussion 930–921.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Ramachandran Venkitaraman
    • 1
  • Karen Thomas
    • 2
  • Phillip Grace
    • 3
  • David P. Dearnaley
    • 4
  • Alan Horwich
    • 4
  • Robert A. Huddart
    • 4
  • Christopher C. Parker
    • 4
  1. 1.Department of Clinical OncologyIpswich Hospital NHS TrustIpswichUK
  2. 2.Computing Department, Urology UnitRoyal Marsden NHS Foundation TrustSuttonUK
  3. 3.HFL Limited, FordhamCambridgeUK
  4. 4.Academic Unit of Radiotherapy & OncologyInstitute of Cancer ResearchSurreyUK

Personalised recommendations