Advertisement

Blood Flow and Oxygenation Status of Prostate Cancers

  • Peter Vaupel
  • Debra K. Kelleher
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 765)

Abstract

Hypoxia is a characteristic of many solid tumors, can lead to the development of an aggressive phenotype and acquired treatment resistance, and is an independent, adverse prognostic indicator. In this literature review, we show that hypoxia is also a typical feature in prostate cancer (PC), the most commonly diagnosed cancer among men in most western countries. Data on blood flow (a major determinant of oxygenation status in malignancies) and on the oxygenation status (as assessed by O2-sensitive electrodes) are presented. Where possible, data on prostate cancers are compared to normal prostate (NP) tissue and benign prostate hyperplasia (BPH). The average blood flow rate in NP is 0.21 vs. 0.28 mL/g/min in BPH. Blood flow in PC is approximately three times higher than in NP (mean flow: 0.64 mL/g/min) and shows pronounced intra- and inter-tumor variability. Despite relatively high flow rates in PC, the overall mean pO2 in cancers is 6 mmHg compared to 26 mmHg in NP. As was the case with blood flow, tissue oxygenation was extremely heterogeneous with no clear dependency on a series of tumor (Gleason score, clinical size, androgen deprivation) and patient characteristics (serum PSA levels, age).

Keywords

Prostate Blood flow Oxygenation 

References

  1. 1.
    Vaupel P (2009) Physiological mechanisms of treatment resistance. In: Molls M, Vaupel P, Nieder C et al (eds) The impact of tumor biology on cancer treatment and multidisciplinary strategies. Springer, Berlin, Heidelberg, pp 273–290CrossRefGoogle Scholar
  2. 2.
    Vaupel P (2008) Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. Oncologist 13(suppl 3):21–36CrossRefPubMedGoogle Scholar
  3. 3.
    Vaupel P (2004) Tumor microenvironmental physiology and its implications for radiation oncology. Semin Radiat Oncol 14:198–206CrossRefPubMedGoogle Scholar
  4. 4.
    Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. Oncologist 9:10–17CrossRefPubMedGoogle Scholar
  5. 5.
    Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239CrossRefGoogle Scholar
  6. 6.
    Vaupel P, Mayer A, Hoeckel M (2004) Tumor hypoxia and malignant progression. Methods Enzymol 381:335–354CrossRefPubMedGoogle Scholar
  7. 7.
    Hoeckel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93:266–276CrossRefGoogle Scholar
  8. 8.
    Hoeckel M, Knoop C, Schlenger K et al (1993) Intra-tumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 26:45–50CrossRefGoogle Scholar
  9. 9.
    Hoeckel M, Schlenger K, Aral B et al (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515Google Scholar
  10. 10.
    Siegel R, Ward E, Brawley O et al (2011) Cancer statistics 2011. CA Cancer J Clin 61:212–236CrossRefPubMedGoogle Scholar
  11. 11.
    Inaba T (1992) Quantitative measurements of prostatic blood flow and blood volume by positron emission tomography. J Urol 148:1457–1460CrossRefPubMedGoogle Scholar
  12. 12.
    Bolmsjö M, Sturesson C, Wagrell L et al (1998) Optimizing transurethral microwave thermotherapy: a model for studying power, blood flow, temperature variations and tissue destruction. Br J Urol 81:811–816CrossRefPubMedGoogle Scholar
  13. 13.
    Harvey CJ, Blomley MJK, Dawson P et al (2001) Functional CT imaging of the acute hyperemic response to radiation therapy of the prostate gland: early experience. J Comput Assist Tomogr 25:43–49CrossRefPubMedGoogle Scholar
  14. 14.
    Hendersen E, Milosevic MF, Haider MA et al (2003) Functional CT imaging of prostate cancer. Phys Med Biol 48:3085–3100CrossRefGoogle Scholar
  15. 15.
    Kershaw LE, Logue JP, Hutchinson CE et al (2008) Late tissue effects following radiotherapy and neoadjuvant hormone therapy of the prostate measured with quantitative magnetic resonance imaging. Radiother Oncol 88:127–134CrossRefPubMedGoogle Scholar
  16. 16.
    Buckley DL, Roberts C, Parker GJM et al (2004) Prostate cancer: evaluation of vascular characteristics with dynamic contrast-enhanced T1-weighted MR imaging—initial experience. Radiology 233:709–715CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Franiel T, Lüdemann L, Rudolph B et al (2009) Prostate MR imaging: tissue characterization with pharmacokinetic volume and blood flow parameters and correlation with histologic parameters. Radiology 252:101–108CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Toma H, Nakamura R, Onitsuka S et al (1988) Effect of endocrine treatment on prostatic blood flow in patients with prostatic adenocarcinoma. J Urol 140:91–95CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Franiel T, Lüdemann L, Lutz MS et al (2008) Evaluation of normal prostate tissue, chronic prostatitis, and prostate cancer by quantitative perfusion analysis using a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence. Invest Radiol 43:481–487CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ives EP, Burke MA, Edmonds PR et al (2005) Quantitative computed tomography perfusion of prostate cancer: correlation with whole-mount pathology. Clin Prostate Cancer 4:109–112CrossRefPubMedGoogle Scholar
  21. 21.
    Mitterberger M, Aigner F, Pinggera GM et al (2010) Contrast-enhanced colour Doppler-targeted prostate biopsy: correlation of a subjective blood-flow rating scale with the histopathological outcome of the biopsy. BJU Int 106:1315–1318CrossRefPubMedGoogle Scholar
  22. 22.
    Alonzi R, Padhani AR, Taylor NJ et al (2011) Antivascular effects of neoadjuvant androgen deprivation for prostate cancer: an in vivo human study using susceptibility and relaxivity dynamic MRI. Int J Radiat Oncol Biol Phys 80:721–727CrossRefPubMedGoogle Scholar
  23. 23.
    Franiel T, Hamm B, Hricak H (2011) Dynamic contrast-enhanced magnetic resonance imaging and pharmacokinetic models in prostate cancer. Eur Radiol 21:616–626CrossRefPubMedGoogle Scholar
  24. 24.
    Movsas B, Chapman JD, Horwitz EM et al (1999) Hypoxic regions exist in human prostate carcinoma. Urology 53:11–18CrossRefPubMedGoogle Scholar
  25. 25.
    Vaupel P, Hoeckel M, Mayer A (2007) Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal 9:1221–1235CrossRefPubMedGoogle Scholar
  26. 26.
    Rasey JS, Koh WJ, Evans ML et al (1996) Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36:417–428CrossRefPubMedGoogle Scholar
  27. 27.
    Chan N, Milosevic M, Bristow RG (2007) Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies. Future Oncol 3:329–341CrossRefPubMedGoogle Scholar
  28. 28.
    Movsas B, Chapman JD, Greenberg RE et al (2000) Increasing levels of hypoxia in prostate carcinoma correlate significantly with increasing clinical stage and patient age. Cancer 89:2018–2024CrossRefPubMedGoogle Scholar
  29. 29.
    Parker C, Milosevic M, Toi A et al (2004) Polarographic electrode study of tumor oxygenation in clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 58:750–757CrossRefPubMedGoogle Scholar
  30. 30.
    Milosevic M, Chung P, Parker C et al (2007) Androgen withdrawal in patients reduces prostate cancer hypoxia: implications for disease progression and radiation response. Cancer Res 67:6022–6025CrossRefPubMedGoogle Scholar
  31. 31.
    Anastasiadis AG, Stisser BC, Ghafar MA et al (2002) Tumor hypoxia and the progression of prostate cancer. Curr Urol Rep 3:222–228CrossRefPubMedGoogle Scholar
  32. 32.
    Cvetkovic D, Movsas B, Dicker AP et al (2001) Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer. Urology 57:821–825CrossRefPubMedGoogle Scholar
  33. 33.
    Movsas B, Chapman JD, Hanlon AL et al (2002) Hypoxic prostate/muscle pO2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings. Urology 60:634–639CrossRefGoogle Scholar
  34. 34.
    Zhong H, de Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res 59:5830–5835PubMedGoogle Scholar
  35. 35.
    Du ZX, Fujiyama C, Chen YX et al (2003) Expression of hypoxia-inducible factor 1α in human normal, benign, and malignant prostate tissue. Chin Med J 116:1936–1939PubMedGoogle Scholar
  36. 36.
    Green MML, Hiley CT, Shanks JH et al (2007) Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome. Int J Radiat Oncol Biol Phys 67:84–90CrossRefPubMedGoogle Scholar
  37. 37.
    Ferrer FA, Miller LJ, Andrawis RI et al (1997) Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vivo expression of VEGF by human prostate cancer cells. J Urol 157:2329–2333CrossRefPubMedGoogle Scholar
  38. 38.
    Jans J, van Dijk JH, van Scheiven S et al (2010) Expression and localization of hypoxia proteins in prostate cancer: prognostic implications after radical prostatectomy. Urology 75:786–792CrossRefGoogle Scholar
  39. 39.
    Vergis R, Corbishley CM, Norman AR et al (2008) Intrinsic markers of tumour hypoxia and angiogenesis in localized prostate cancer and outcome of radical treatment: a retrospective analysis of two randomized radiotherapy trials and one surgical cohort study. Lancet Oncol 9:342–351CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Muramoto P et al (2002) H215O positron emission tomography validation of semiquantitative prostate blood flow determined by double-echo dynamic MRI: a preliminary study. J Comput Assist Tomogr 26:510–514CrossRefGoogle Scholar
  41. 41.
    Venn SN, Hughes SW, Montgomery BSI et al (1996) Heating characteristics of a 434 MHz transurethral system for the treatment of BPH and interstitial thermometry. Int J Hyperthmia 12:271–278CrossRefGoogle Scholar
  42. 42.
    Franiel T, Lüdemann L, Taupitz M et al (2009) Pharmacokinetic MRI of the prostate: parameters for differentiating low-grade and high-grade prostate cancer. Fortschr Röntgenstr 181:536–542CrossRefGoogle Scholar
  43. 43.
    van Vulpen M, Raaymakers BW, de Leeuw AAC et al (2002) Prostate perfusion in patients with locally advanced prostate carcinoma treated with different hyperthermia techniques. J Urol 168:1597–1602CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Radiotherapy and RadiooncologyKlinikum rechts der Isar, Technische Universität MünchenMunichGermany
  2. 2.Institute of Functional and Clinical AnatomyUniversity Medical CenterMainzGermany

Personalised recommendations