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Management of Rising Prostate-specific Antigen After a Negative Biopsy

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Abstract

Prostate biopsy remains one of the most commonly performed urologic office procedures. A significant percentage of men with a negative result may have unrecognized disease. Inadequate biopsy strategies or findings of high-grade prostatic intraepithelial neoplasia or atypia increase this likelihood. The term “negative biopsy” may be misleading. Traditional sextant biopsy is inaccurate and extended- or saturation-biopsy protocols miss small cancers. A rising prostate-specific antigen (PSA) after a negative prostate biopsy may indicate undiagnosed cancer. Magnetic resonance imaging (MRI) and template-guided biopsy have been proposed as diagnostic adjuncts in this setting. Medical manipulation has met with limited acceptance in this setting. In the presence of a rising PSA after a negative biopsy a low threshold for repeat biopsy should be entertained. Saturation biopsy increases cancer detection, especially in patients with more than two prior biopsies. Adjuncts to improve cancer detection, such as administration of 5-α-reductase inhibitors and MRI, are promising.

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References

Papers of particular interest, published recently, have been highlighted as: •   Of importance

  1. Hodge KK, McNeal JE, Stamey TA. Ultrasound guided transrectal core biopsies of the palpably abnormal prostate. J Urol. 1989;142:66–70.

    PubMed  CAS  Google Scholar 

  2. Hodge KK, McNeal JE, Terris MK, et al. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol. 1989;142:71–4.

    PubMed  CAS  Google Scholar 

  3. Keetch DW, Catalona WJ, Smith DS. Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values. J Urol. 1994;151:1571–4.

    PubMed  CAS  Google Scholar 

  4. Haas GP, Delongchamps NP, Jones RF, et al. Needle biopsies on autopsy prostates: sensitivity of cancer detection based on true prevalence. J Natl Cancer Inst. 2007;99:1484–9.

    Article  PubMed  Google Scholar 

  5. Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2006;98:529–34.

    Article  PubMed  Google Scholar 

  6. Nguyen CT, Yu C, Moussa AS, et al. Performance of the prostate cancer prevention trial risk calculator in a contemporary cohort of men screened for prostate cancer and diagnosed with extended prostate biopsy schemes. J Urol. 2010;183:529–33.

    Article  PubMed  Google Scholar 

  7. Hong YM, Lai FC, Chon CH, et al. Impact of prior biopsy scheme on pathologic features of cancers detected on repeat biopsies. Urol Oncol. 2004;22:7–10.

    Article  PubMed  Google Scholar 

  8. Baccala AA, Moussa AS, Hernandez AV, et al. Risk factors and predictors of prostate cancer in men with negative repeat saturation biopsy. UroToday International Journal. 2010, in press.

  9. Schoenfield L, Jones JS, Zippe CD, et al. The incidence of high-grade prostatic intraepithelial neoplasia and atypical glands suspicious for carcinoma on first-time saturation needle biopsy, and the subsequent risk of cancer. BJU Int. 2007;99:770–4.

    Article  PubMed  CAS  Google Scholar 

  10. Abouassaly R, Tan N, Moussa A, Jones JS. Risk of prostate cancer after diagnosis of atypical glands suspicious for carcinoma on saturation and traditional biopsies. J Urol. 2008;180:911–4.

    Article  PubMed  Google Scholar 

  11. • Wolters T, van der Kwast TH, Vissers CJ, et al. False-negative prostate needle biopsies: frequency, histopathologic features, and follow-up. Am J Surg Pathol. 2010;34:35–43. This article established that histological examination of biopsy material may miss cancer in a real percentage of patients. The implication is that a second pathological opinion might be of value, at least in equivocal cases.

  12. Lefkowitz GK, Sidhu GS, Torre P, Lepor H, Taneja SS. Is repeat prostate biopsy for high-grade prostatic intraepithelial neoplasia necessary after routine 12-core sampling? Urology. 2001;58:999–1003.

    Article  PubMed  CAS  Google Scholar 

  13. McNeal JE, Redwine EA, Freiha FS, et al. Zonal distribution of prostatic adenocarcinoma. Correlation with histologic pattern and direction of spread. Am J Surg Pathol. 1988;12:897–906.

    Article  PubMed  CAS  Google Scholar 

  14. Bazinet M, Karakiewicz PI, Aprikian AG, et al. Value of systematic transition zone biopsies in the early detection of prostate cancer. J Urol. 1996;155:605–6.

    Article  PubMed  CAS  Google Scholar 

  15. Terris MK, Pham TQ, Issa MM, et al. Routine transition zone and seminal vesicle biopsies in all patients undergoing transrectal ultrasound guided prostate biopsies are not indicated. J Urol. 1997;157:204–6.

    Article  PubMed  CAS  Google Scholar 

  16. Epstein JI, Walsh PC, Sauvageot J, et al. Use of repeat sextant and transition zone biopsies for assessing extent of prostate cancer. J Urol. 1997;158:1886–90.

    Article  PubMed  CAS  Google Scholar 

  17. Patel AR, Jones JS, Rabets J, et al. Parasagittal biopsies add minimal information in repeat saturation prostate biopsy. Urology. 2004;63:87–9.

    Article  PubMed  Google Scholar 

  18. Takashima R, Egawa S, Kuwao S, et al. Anterior distribution of Stage T1c nonpalpable tumors in radical prostatectomy specimens. Urology. 2002;59:692–7.

    Article  PubMed  Google Scholar 

  19. Bott SR, Young MP, Kellett MJ, et al. Anterior prostate cancer: is it more difficult to diagnose? BJU Int. 2002;89:886–9.

    Article  PubMed  CAS  Google Scholar 

  20. • Bouyé S, Potiron E, Puech P, et al. Transition zone and anterior stromal prostate cancers: zone of origin and intraprostatic patterns of spread at histopathology. Prostate. 2009;69:105–113. This article demonstrated that anterior cancers may be missed by biopsy but detected by MRI.

  21. Wright JL, Ellis WJ. Improved prostate cancer detection with anterior apical prostate biopsies. Urol Oncol. 2006;24:492–5.

    Article  PubMed  Google Scholar 

  22. Moussa AS, Meshref A, Schoenfield L, et al. Importance of additional “extreme” anterior apical needle biopsies in the initial detection of prostate cancer. Urology, accepted for publication. 2010.

  23. Stamey TA. Making the most out of six systematic sextant biopsies. Urology. 1995;45:2–12.

    Article  PubMed  CAS  Google Scholar 

  24. Keetch DW, Catalona WJ, Smith DS. Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values. J Urol. 1994;151:1571–4.

    PubMed  CAS  Google Scholar 

  25. Babaian RJ, Toi A, Kamoi K, et al. A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol. 2000;163:152–7.

    Article  PubMed  CAS  Google Scholar 

  26. Eskew LA, Bare RL, McCullough DL. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol. 1997;157:199–202.

    Article  PubMed  CAS  Google Scholar 

  27. Presti Jr JC, Chang JJ, Bhargava V, et al. The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial. J Urol. 2000;163:163–6.

    Article  PubMed  Google Scholar 

  28. Gore JL, Shariat SF, Miles BJ, et al. Optimal combinations of systematic sextant and laterally directed biopsies for the detection of prostate cancer. J Urol. 2001;165:1554–9.

    Article  PubMed  CAS  Google Scholar 

  29. Presti Jr JC, O’Dowd GJ, Miller MC, et al. Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study. J Urol. 2003;169:125–9.

    Article  PubMed  Google Scholar 

  30. Berger AP, Gozzi C, Steiner H, et al. Complication rate of transrectal ultrasound guided prostate biopsy: a comparison among 3 protocols with 6, 10 and 15 cores. J Urol. 2004;171:1478–80.

    Article  PubMed  Google Scholar 

  31. • Ching CB, Moussa AS, Li J, et al. Does transrectal ultrasound probe really matter? End-fire versus side-fire: prostate cancer detection rates. J Urol. 2009, 181:2077–2082. This article showed that end-fire probes can traverse the gland and identify anterior or apical tumors more accurately than more common side-fire probes.

  32. Karakiewicz PI, Bazinet M, Aprikian AG, et al. Outcome of sextant biopsy according to gland volume. Urology. 1997;49:55–9.

    Article  PubMed  CAS  Google Scholar 

  33. Djavan B, Zlotta AR, Remzi M, et al. Total and transition zone prostate volume and age: how do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection? Urology. 1999;54:846–52.

    Article  PubMed  CAS  Google Scholar 

  34. Borboroglu PG, Comer SW, Riffenburgh RH, et al. Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies. J Urol. 2000;163:158–62.

    Article  PubMed  CAS  Google Scholar 

  35. Stewart CS, Leibovich BC, Weaver AL, et al. Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol. 2001;166:86–91.

    Article  PubMed  CAS  Google Scholar 

  36. Jones JS, Patel A, Schoenfield L, et al. Saturation technique does not improve cancer detection as an initial prostate biopsy strategy. J Urol. 2006;175:485–8.

    Article  PubMed  Google Scholar 

  37. Epstein JI, Sanderson H, Carter HB, Scharfstein DO. Utility of saturation biopsy to predict insignificant cancer at radical prostatectomy. Urology. 2005;66:356–60.

    Article  PubMed  Google Scholar 

  38. Bott SR, Henderson A, Halls JE, et al. Extensive transperineal template biopsies of prostate: modified technique and results. Urology. 2006;68:1037–41.

    Article  PubMed  Google Scholar 

  39. Satoh T, Matsumoto K, Fujita T, et al. Cancer core distribution in patients diagnosed by extended transperineal prostate biopsy. Urology. 2005;66:114–8.

    Article  PubMed  Google Scholar 

  40. Moran BJ, Braccioforte MH, Conterato DJ. Re-biopsy of the prostate using a stereotactic transperineal technique. J Urol. 2006;176(4 Pt 1):1376–81.

    Article  PubMed  Google Scholar 

  41. Rabets JC, Jones JS, Patel A, et al. Prostate cancer detection with office based saturation biopsy in a repeat biopsy population. J Urol. 2004;172:94–7.

    Article  PubMed  Google Scholar 

  42. Walz J, Graefen M, Chun FK, et al. High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series. Eur Urol. 2006;50:498–505.

    Article  PubMed  Google Scholar 

  43. de la Taille A, Antiphon P, Salomon L, et al. Prospective evaluation of a 21-sample needle biopsy procedure designed to improve the prostate cancer detection rate. Urology. 2003;61:1181–6.

    Article  PubMed  Google Scholar 

  44. Sciarra A, Panebianco V, Ciccariello M, et al. Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin Cancer Res. 2010;16:1875–83.

    Article  PubMed  CAS  Google Scholar 

  45. Noworolski SM, Vigneron DB, Chen AP, Kurhanewicz J. Dynamic contrast-enhanced MRI and MR diffusion imaging to distinguish between glandular and stromal prostatic tissues. Magn Reson Imaging. 2008;26:1071–80.

    Article  PubMed  Google Scholar 

  46. Puech P, Betrouni N, Makni N, et al. Computer-assisted diagnosis of prostate cancer using DCE-MRI data: design, implementation and preliminary results. Int J Comput Assist Radiol Surg. 2009;4:1–10.

    Article  PubMed  Google Scholar 

  47. Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192–202.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to David A. Levy.

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Levy, D.A., Jones, J.S. Management of Rising Prostate-specific Antigen After a Negative Biopsy. Curr Urol Rep 12, 197–202 (2011). https://doi.org/10.1007/s11934-011-0177-1

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  • DOI: https://doi.org/10.1007/s11934-011-0177-1

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