Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

  • Cormac FarrellyEmail author
  • Priti Lal
  • Scott O. Trerotola
  • Gregory J. Nadolski
  • Micah M. Watts
  • Catherine Mc. Gorrian
  • Thomas J. Guzzo
Clinical Investigation



To correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.

Materials and Methods

In this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.


Mean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.


fPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.


Prostate cancer PSA levels Venous sampling Free PSA 



Grant Support: Study supported with a seed Research Grant: F. Hoffmann- La Roche Ltd. (Roche Diagnostics). 15,000 US Dollar Grant.

Compliance with Ethical Standards

Conflict of interest

This study was funded by a 15,000 US Dollar seed research grant from Roche diagnostics: F. Hoffmann- La Roche Ltd. Author A declares no other potential conflict of interest. Authors Priti Lal, Micah M. Watts, Catherine Mc Gorrian and Thomas J. Guzzo declare that they have no conflicts of interest. Author Scott O. Trerotola declares grants from Vascular Pathways, personal fees from Bard Peripheral Vascular, personal fees from Orbimed, personal fees from Teleflex, personal fees from Cook, personal fees from WL Gore, personal fees from Lutonix and personal fees from Medcomp. These are all outside the submitted work, and there is no conflict of interest. Author Gregory J. Nadolski declares grants from Guerbet, LLC. This is outside the submitted work, and there is no conflict of interest.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2008;58(2):71–96.CrossRefPubMedGoogle Scholar
  2. 2.
    Carrol PR. Early stage prostate cancer-do we have a problem with over-detection, overtreatment or both? J Urol. 2005;173(4):1061–2.CrossRefGoogle Scholar
  3. 3.
    Mouraviev V, Mayes JM, Madden JF, Sun L, Polascik TJ. Analysis of laterality and percentage of tumor involvement in 1386 prostatectomized specimens for selection of unilateral focal cryotherapy. Tech Cancer Res Treat. 2007;6(2):91–6.CrossRefGoogle Scholar
  4. 4.
    Djavan B, Susani M, Bursa B, Basharkhah A, Simak R, Marberger M. Predictability and significance of multifocal cancer in the radical prostatectomy specimen. Techn Urol. 1999;5(3):139–42.CrossRefGoogle Scholar
  5. 5.
    Polascik TJ, Mayers JM, Sun L, Madden JF, Moul JW, Mouraviev V. Pathologic stage 2a and 2b prostate cancer in the recent prostate-specific antigen era: implications for unilateral ablative therapy. Prostate. 2008;68(13):1380–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Turpen R, Rosser CJ. Focal therapy for prostate cancer: revolution or evolution? BMC Urol. 2009;9:2.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Polascik TJ, Mouraviev V. Focal therapy for prostate cancer is a reasonable treatment option in properly selected patients. Urology. 2009;74(4):726–30.CrossRefPubMedGoogle Scholar
  8. 8.
    Eggener SE, Scardino PT, Carroll PR, Zelefsky MJ, Sartor O, Hricak H, for the International task force on prostate cancer and the focal lesion paradigm, et al. Focal therapy for localized prostate cancer: a critical appraisal of rationale and modalities. J Urol. 2007;178(6):2260–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Scardino PT, Abenhaim LL. Focal therapy for prostate cancer: analysis by an international panel. Urology. 2008;72(6 Suppl):S1–2.CrossRefPubMedGoogle Scholar
  10. 10.
    Mendez MH, Joh DY, Gupta R, Polascik TJ. Current trends and new frontiers in focal therapy for localized prostate cancer. Curr Urol Rep. 2015;16(6):35.CrossRefPubMedGoogle Scholar
  11. 11.
    Fitzpatrick JM. PSA measurement in the treatment of BPH. BJU Int. 2004;93(1 Suppl):2–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Wendell-Smith C. Terminology of the prostate and related structures. Clin Anat. 2000;13(3):207–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic diseases. JAMA. 1998;279(19):1542–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Djavan B, Remzi M, Zlotta AR, Ravery V, Hammerer P, Reissigl A, et al. Complexed prostate-specific antigen, complexed prostate-specific antigen density of total and transition zone, complexed/total prostate-specific antigen ratio, free-to-total prostate-specific antigen ratio, density of total and transition zone prostate-specific antigen: results of the prospective multicenter European trial. Urology. 2002;60(4 Suppl 1):4–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Puppo P. Repeated negative prostate biopsies with persistently elevated or rising PSA: a modern urologic dilemma. Eur Urol. 2007;52(3):639–41.CrossRefPubMedGoogle Scholar
  16. 16.
    Jones JS. Management of rising prostate-specific antigen following a negative biopsy. Curr Opin Urol. 2010;20(3):198–203.CrossRefPubMedGoogle Scholar
  17. 17.
    Trock BJ. Circulating biomarkers for discriminating indolent from aggressive disease in prostate cancer active surveillance. Curr Opin Urol. 2014;24(3):293–302.CrossRefPubMedGoogle Scholar
  18. 18.
    Whitesel JA, Donohue RE, Mani JH, Mohr S, Scanavino DJ, Augspurger RR, et al. Acid phosphatase: its influence on the management of carcinoma of the prostate. J Urol. 1984;131(1):70–2.PubMedGoogle Scholar
  19. 19.
    Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al. Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104(2):125–32.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014;384(9959):2027–35.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Pinsky PF, Parnes HL, Andriole G. Mortality and complications after prostate biopsy in the prostate, lung, colorectal and ovarian cancer screening (PLCO) trial. BJU Int. 2014;113(2):254–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Anastasiadis E, van der Meulen J, Emberton M. Hospital admissions after transrectal ultrasound-guided biopsy of the prostate in men diagnosed with prostate cancer: a database analysis in England. Int J Urol. 2015;22(2):181–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Carrol PR. Early stage prostate cancer-do we have a problem with over-detection, overtreatment or both? J Urol. 2005;173(4):1061–2.CrossRefGoogle Scholar
  24. 24.
    Ward JF, Pisters LL. Considerations for patient selection for focal therapy. Ther Adv Urol. 2013;5(6):330–7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lau JH, Drake W, Matson M. The current role of venous sampling in the localization of endocrine disease. Cardiovasc Intervent Radiol. 2007;30(4):555–70.CrossRefPubMedGoogle Scholar
  26. 26.
    Young W, Stanson A, Thompson G, et al. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004;136(6):1227–35.CrossRefPubMedGoogle Scholar
  27. 27.
    Ginsburg M, Christoforidis GA, Zivin SP, Obara P, Wroblewski K, Angelos P, et al. Adenoma localization for recurrent or persistent primary hyperparathyroidism using dynamic four-dimensional CT and venous sampling. J Vasc Interv Radiol. 2015;26(1):79–86.CrossRefPubMedGoogle Scholar
  28. 28.
    Kaltsas G, Mukherjee J, Kola B, Isidori AM, Hanson JA, Dacie JE, et al. Is ovarian and adrenal venous catheterization and sampling helpful in the investigation of hyperandrogenic women? Clin Endocrinol. 2003;59(1):34–43.CrossRefGoogle Scholar
  29. 29.
    Agarwal MD, Trerotola SO. Combined adrenal and ovarian venous sampling to localize an androgen producing tumor. Cardiovasc Intervent Radiol. 2010;33(6):1266–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Lilja H. Biology of prostate-specific antigen. Urology. 2003;62(5 Suppl 1):27–33.CrossRefPubMedGoogle Scholar
  31. 31.
    Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, et al. Prostate specific antigen best practice statement: 2009 update. J Urol. 2013;189(1 Suppl):2–11.CrossRefGoogle Scholar
  32. 32.
    Batson OV. The function of the vertebral veins and their role in the spread of metastases. Ann Surg. 1940;112(1):138–49.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Batson OV. The vertebral vein system: Caldwell Lecture, 1956. Am J Roentgenol Radium Ther Nucl Med. 1957;78(2):195–212.PubMedGoogle Scholar
  34. 34.
    Suzuki T, Kurokawa K, Jimbo H, Hayashi M, Sekihara T, Takahashi H, et al. The role of intraabdominal pressure in venous blood drainage from the prostate into the vertebral vein system. Jpn J Physiol. 1993;43(5):697–708.CrossRefPubMedGoogle Scholar
  35. 35.
    Franks LM. The spread of prostatic carcinoma to the bones. J Pathol Bacteriol. 1953;66:91–3.CrossRefPubMedGoogle Scholar
  36. 36.
    McCormack RT, Rittenhouse HG, Finlay JA, Sokoloff RL, Wang TJ, Wolfert RL, et al. Molecular forms of prostate-specific antigen and the human kallikrein gene family: a new era. Urology. 1995;45(5):729–44.CrossRefPubMedGoogle Scholar
  37. 37.
    Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic diseases. JAMA. 1998;279(19):1542–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Richardson TD, Wojno KJ, Liang LW, Giacherio DA, England BG, Henricks WH, et al. Half-life determination of serum free prostate-specific antigen following radical retropubic prostatectomy. Urology. 1996;48(6A Suppl):40–4.CrossRefPubMedGoogle Scholar
  39. 39.
    Turkbey B, Albert PS, Kurdziel K, Choyke PL. Imaging localized prostate cancer: current approaches and new developments. AJR. 2009;192(6):1471–80.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hamoen EH, de Rooij M, Witjes JA, Barentsz JO, Rovers MM. Use of the prostate imaging reporting and data system (PI-RADS) for prostate cancer detection with multiparametric magnetic resonance imaging: a diagnostic meta-analysis. Eur Urol. 2015;67(6):1112–21.CrossRefPubMedGoogle Scholar
  41. 41.
    Blomqvist L, Carlsson S, Gjertsson P, Heintz E, Hultcrantz M, Mejare I, et al. Limited evidence for the use of imaging to detect prostate cancer: a systematic review. Eur J Radiol. 2014;83(9):1601–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Schoots IG, Petrides N, Giganti F, Bokhorst LP, Rannikko A, Klotz L, et al. Magnetic resonance imaging in active surveillance of prostate cancer: a systematic review. Eur Urol. 2015;67(4):627–36.CrossRefPubMedGoogle Scholar
  43. 43.
    Ross AE, D’Amico AV, Freedland SJ. Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer. Prostate Cancer Prostatic Dis. 2015. doi: 10.1038/pcan.2015.31.PubMedCentralGoogle Scholar
  44. 44.
    Falzarano SM, Ferro M, Bollito E, Klein EA, Carrieri G, Magi-Galluzzi C. Novel biomarkers and genomic tests in prostate cancer: a critical analysis. Minerva Urol Nefrol. 2015;67(3):211–31.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2016

Authors and Affiliations

  • Cormac Farrelly
    • 1
    • 5
    Email author
  • Priti Lal
    • 2
  • Scott O. Trerotola
    • 1
  • Gregory J. Nadolski
    • 1
  • Micah M. Watts
    • 1
  • Catherine Mc. Gorrian
    • 3
  • Thomas J. Guzzo
    • 4
  1. 1.Division of Interventional Radiology, Department of RadiologyHospital of the University of Pennsylvania, Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  3. 3.University College Dublin School of Medicine & Medical ScienceMater Misericordiae University HospitalDublinIreland
  4. 4.Department of Urology and SurgeryUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  5. 5.Department of Radiology, Level 2 Whitty WingMater Misericordiae University HospitalDublinIreland

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