Comparison between Use of PSA Kinetics and Bone Marrow Micrometastasis to Define Local or Systemic Relapse in Men with Biochemical Failure after Radical Prostatectomy for Prostate Cancer

  • Published : 2016.01.11


Background: Treatment of biochemical failure after radical prostatectomy for prostate cancer is largely empirically based. The use of PSA kinetics has been used as a guide to determine local or systemic treatment of biochemical failure. We here compared PSA kinetics with detection of bone marrow micrometastasis as methods to determine local or systemic relapse. Materials and Methods: A transversal study was conducted of men with biochemical failure, defined as a serum PSA >0.2ng/ml after radical prostatectomy. Consecutive patients having undergone radical prostatectomy and with biochemical failure were enrolled and clinical and pathological details were recorded. Bone marrow biopsies were obtained from the iliac crest and touch prints made, micrometastasis (mM) being detected using anti-PSA. The clinical parameters of total serum PSA, PSA velocity, PSA doubling time and time to biochemical failure, age, Gleason score and pathological stage were registered. Results: A total of 147 men, mean age $71.6{\pm}8.2years$, with a median time to biochemical failure of 5.5 years (IQR 1.0-6.3 years) participated in the study. Bone marrow samples were positive for micrometastasis in 98/147 (67%) of patients at the time of biochemical failure. The results of bone marrow micrometastasis detected by immunocytochemistry were not concordant with local relapse as defined by PSA velocity, time to biochemical failure or Gleason score. In men with a PSA doubling time of < six months or a total serum PSA of >2,5ng/ml at the time of biochemical failure the detection of bone marrow micrometastasis was significantly higher. Conclusions: The detection of bone marrow micrometastasis could be useful in defining systemic relapse, this minimally invasive procedure warranting further studies with a larger group of patients.


Prostate cancer;biochemical failure;bone marrow micrometastasis;systemic or local relapse


  1. Bain BJ (2003). Bone marrow biopsy morbidity and mortality. Br J Haematol, 121, 949-51
  2. Amling CL, Bergstralh EJ, Blute ML, et al (2001). Defining PSA progression after radical prostatectomy. What is the most appropriate cutoff? J Urol, 165, 1146
  3. Aus G, Abbou CC, Bolla M, et al (2006). Guidelines on Prostate Cancer. Ed EUA; Arnhem, EAU Guidelines Office. Chapter, 1, 106
  4. 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.
  5. Dotan ZA, Bianco FJ Jr, Rabini F, et al (2005). Pattern of PSA failure dictates the probability of a positive bone scan in patients with an increasing PSA after radical prostatectomy. J Clin Oncol, 23, 1962-8
  6. Freedland SJ, Sutter ME, Dorey F, et al (2003). Defining the ideal cutoff point for determining PSA recurrence after radical prostatectomy. Urol, 61, 365-369
  7. Freedland SJ, Humphries EB, Mangold LA, et al (2007). Death in patients with recurrent prostate cancer after radical prostatectomy. PSA doubling time subgroups and their associated contributions to all cause mortality. J Clin Oncol, 25, 1765-71
  8. Hamilton RJ, Aronson WJ, Terris MK, et al (2008). Limitations of PSA doubling time following biochemical recurrence after radical prostatectomy: results from the SEARCH database. J Urol, 179, 1785-9.
  9. Han M, Partin AW, Zahurak MW, et al (2003). Biochemical (PSA) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol, 169, 517-23
  10. Murray NP, Reyes E, Tapia P, et al (2012). Redefining micrometastasis in prostate cance-a comparison of circulating prostate cells, bone marrow disseminated tumor cells and micrometastasis: implications in determining local or systemic treatment for biochemcial failure after radical prostatectomy. Int J Mol Med, 30, 896-904
  11. NCCN (2014) prostate cancer guidelines. NICE UK prostate cancer guidelines 2015.
  12. Okotie OT, Aronson WJ, Wieder JA, et al (2004). Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. J Urol, 171, 2260-4
  13. Partin AW, Pearson JD, Landis PK, et al (1994). Evaluation of serum PSA velocity after radical prostatectomy to distinguish local recurrence from systemic metastasis. Urol, 43, 649-59
  14. Pound CR, Partin AW, Epstein JI, et al (1997). PSA after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control. Urol Clin North Amm, 24, 395-406
  15. Scattoni V, Montorsi F, Picchio L, et al (2004). Diagnosis of locasl recurrence after radical prostatectomy. BJU Int, 93, 680-8
  16. Wood DP, Banerjee M (1997). Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease free survival. J Clin Oncol, 15, 3451-7.

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