Efficacy of Using Sequential Primary Circulating Prostate Cell Detection for Initial Prostate Biopsy in Men Suspected of Prostate Cancer

  • Published : 2016.07.01


Background: Sequential use of circulating prostate cell (CPC) detection has been reported to potentially decrease the number of unnecessary prostate biopsies in men suspected of prostate cancer. In order to determine the real world effectiveness of the test, we present a prospective study of men referred to two hospitals from primary care physicians, one using CPC detection to determine the necessity of prostate biopsy the other not doing so. Materials and Methods: Men with a suspicion of prostate cancer because of elevated PSA >4.0ng/ml or abnormal DRE were referred to Hospitals A or B. In Hospital A all underwent 12 core TRUS biopsy, in Hospital B only men CPC (+), with mononuclear cells obtained by differential gel centrifugation identified using double immunomarking with anti-PSA and anti-P504S, were recommended to undergo TRUS biopsy. Biopsies were classifed as cancer or no-cancer. Diagnostic yields were calculated, including the number of posible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: Totals of 649 men attended Hospital A, and 552 men attended Hospital B; there were no significant differences in age or serum PSA levels. In Hospital A, 228 (35.1%) men had prostate cancer detected, CPC detection had a sensitivity of 80.7%, a specificity of 88.6%, and a negative predictive value of 89.5%. Some 39/44 men CPC negative with a positive biopsy had low grade small volume tumors. In Hospital B, 316 (57.2%) underwent biopsy. There were no significant differences between populations in terms of CPC and biopsy results. The reduction in the number of biopsies was 40%. Conclusions: The use of sequential CPC testing in the real world gives a clear decision structure for patient management and can reduce the number of biopsies considerably.


  1. Murray NP. Reyes E, Orellana N, et al (2015). Prostate cancer screening in the fit Chilean elderly: a head to head comparison of total serum PSA versus age adjusted PSA versus primary circulating prostate cells to detect prostate cancer at initial biopsy. Asian Pac J Cancer Prev, 16, 601-6.
  2. Murray NP, Reyes E, Orellana N, et al (2014a). A comparative performance analysis of total PSA, percentage free PSA, PSA velocity and PSA density versus the detection of primary circulating prostate cells in predicting initial biopsy findings in Chilean men. Biomed Res Int, 2014, 676572
  3. Murray NP, Reyes E, Fuentealba C et al (2015a). Head to head comparison ofthe Montreal nomogram with the detection of primary malignant circulating prostate cells to predict prostate cancer at initial biopsy in Chilean men with suspicion of prostate cancer. Urol Oncol, 33, 19-25.
  4. Pavlakis K, Stravodimos K, Kapetanakis T, et al (2010). Evaluation of routine applications of P504S, $34{\beta}E12$ and p63 immunostaining on 250 prostate needle biopsy specimens. Int Urol Nephrol, 42, 325-30.
  5. Ploussard G, Nicolaiew N, Marchand C, et al (2013). Risk of repeat biopsy and prostate cancer detection after an initial extended negative biopsy: longitudinal follow up from a prospective trail. BJU Int, 111, 988-996.
  6. Rietbergen JB, Kruger AE, Krause R, et al (1997). Complications of transrectal ultrasound guided systematic sextant biopsies of prostate: evaluation of complication rates and risk factors within a population based screening population. Urol, 49, 875-80.
  7. Rubin MA, Zhou M, Dhanasekaran SM, et al (2001). alphamethylacyl Coenzyme-A racemase as a tissue biomarker for prostate cancer. JAMA, 287, 1662-70.
  8. Schwarzenbach H, Alix-Panabieres C, Muller I, et al (2009). Cell free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer. Clin Cancer Res, 15, 1032-8
  9. Sullivan SD, Watkins J, Sweet B, et al (2009). Health technology assessment in health care decisions in the United States. Value Health, 2, 39-44.
  10. Weinstein MC, Skinner JA (2010). Comparative effectiveness and health care spending-implications for reform. N Eng J Med, 362, 460-5.
  11. Welch HG, Schwartz LM, Woloshin S (2005). PSA levels in the United States. Implications of various definitions for abnormal. J Natl Cancer Inst, 97, 1132-7.
  12. Wennberg J, Gittelsohn J (1973). Small area variations in health care delivery. Science, 182, 1102-8.
  13. Xue X, Teare MD, Holen I, et al (2009). Optimizing the yield and utility of circulating cell free DNA from plasma and serum. Clin Chim Acta, 404, 100-4.
  14. Altimaru A, Grigioni AD, Benedettini E, et al (2008). Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer. Am J Clin Pathol, 129, 756-62.
  15. Bastian PJ, Palapattu GS, Yegnasubramanian S et al (2007). Prognostic value of preoperative serum cell-free circulating DNA in men with prostate cancer undergoing radical prostatectomy. Clin Cancer Res, 13, 5361-7.
  16. Boddy JL, Gal S, Malone PR, et al (2005). Prospective study of quantitation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin Cancer Res, 11, 1394-9.
  17. Borgen E, Naume B, Nesland JM, et al (1999). Standardization of the immunocytochemical detection of cancer cells in BM and blood. I. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy, 1, 377-88.
  18. Campbell MF, Wein AJ, Kavoussi LR, Campbell's Urology (2011). V, Section II, chapter 3.
  19. Davis JW, Nakanishi H, Kumar VS, et al (2008). Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer. J Urol, 179, 2187-91.
  20. Ellinger J, Bastian PJ, Haan KI et al (2008). Noncancerous PTGS2 DNA fragments of apoptotic origin in sera of prostate cancer patients qualify as diagnostic and prognostic indicators. Int J Cancer, 122, 138-43.
  21. Ellinger J, Muller SC, Stadler TC, et al (2011). The role of cell free circulating DNA in the diagnosis and prognosis of prostate cancer. Urol Oncol, 29, 124-9.
  22. Epstein JI, Walsh PC, Carmichael M, et al (1994). Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA, 271, 368-374.
  23. Eschwege P, Moutereau S, Droupy S, et al (2009). Prognostic value of prostate circulating cells detection in prostate cancer patients: a prospective study. Br J Cancer, 100, 608-10.
  24. Fang J, Mettler EJ, Landis P, et al (2001) Low level of PSA predicts long term risk of prostate cancer: results from the Baltimore Longitudinal Study on Aging. Urol, 58, 413-416.
  25. Gordian E, Ramachandran K, Reis IM, et al (2010). Serum free circulating DNA is a useful biomarker to distinguish benign versus malignant prostate disease. Cancer Epidemiol Biomarkers Prev, 19, 1984-91.
  26. Grosse SD, Khoury MJ (2006). What is the clinical utility of genetic testing? Genetics Med, 8, 448-450.
  27. Horninger W, Berger AP, Rogatsch H, et al (2004). Characteristics of prostate cancer detected al low PSA levels. Prostate, 58, 232-7.
  28. Institute of Medicine of the National Academies (2007): Learning what works best; the nation's need for evidence on comparative effectiveness in healthcare. Institute of Medicine of the National Academies: Washington DC, USA.
  29. Jung K, Stephan C, Lewandowski M, et al (2004). Increased cell free DNA in plasma of patients with metastatic spread in prostate cancer. Cancer Lett, 205, 173-180.
  30. Murray NP, Reyes E, Orellana N, et al (2013). Cost-benefit of incorporating the detection of circulating prostate cells in ascreening programme for prostate cancer. Arch Esp Urol, 66, 277-286.
  31. Murray NP, Reyes E, Fuentealba C, et al (2014) Extended use of P504S primary circulating prostate cells to determine the need for initial prostate biosy in a prostate screening program in Chile. Asian Pac J Cancer Prev, 15, 9335-9.