Prostate Biopsy in Active Surveillance Protocols: Immediate Re-biopsy and Timing of Subsequent Biopsies

  • Jonathan H. Wang
  • Tracy M. Downs
  • E. Jason Abel
  • Kyle A. Richards
  • David F. Jarrard
Prostate Cancer (S Prasad, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Prostate Cancer


Purpose of Review

This manuscript reviews contemporary literature regarding prostate cancer active surveillance (AS) protocols as well as other tools that may guide the management of biopsy frequency and assess the possibility of progression in low-risk prostate cancer.

Recent Findings

There is no consensus regarding the timing of surveillance biopsies; however, an immediate repeat biopsy within 12 months of diagnosis for patients considering AS confirms patients who have favorable risk disease yet also identifies patients who were undersampled initially. Studies regarding multiparametric MRI, nomograms, and biomarkers show promise in risk stratifying and counseling patients during AS. Further studies are needed to determine if these supplemental tests can decrease the frequency of surveillance biopsies.


An immediate re-biopsy can help to reduce the risk of missing clinically significant disease. Other clinical tools, including mpMRI, exist that can be used as an adjunct to counsel patients and guide a personalized discussion regarding the frequency of surveillance biopsies.


Prostate cancer Active surveillance Prostate biopsy Repeat biopsy Multiparametric MRI 


Compliance with Ethical Standards

Conflict of Interest

Jonathan H. Wang, Tracy M. Downs, E. Jason Abel, Kyle A. Richards, and David F. Jarrard each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61:1079–92.CrossRefPubMedGoogle Scholar
  3. 3.
    Schröder FH, Hugosson J, Roobol MJ, 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;384:2027–35.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Heijnsdijk EAM, der Kinderen A, Wever EM, Draisma G, Roobol MJ, de Koning HJ. Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer. Br J Cancer. 2009;101:1833–8.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Siegel R, Miller K, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:29.Google Scholar
  6. 6.
    Gorin MA, Eldefrawy A, Ekwenna O, Soloway MS. Active surveillance for low-risk prostate cancer: knowledge, acceptance and practice among urologists. Prostate Cancer Prostatic Dis. 2012;15:177–81.CrossRefPubMedGoogle Scholar
  7. 7.
    • Loeb S, Walter D, Curnyn C, Gold HT, Lepor H, Makarov DV. How active is active surveillance? Intensity of followup during active surveillance for prostate cancer in the United States. J Urol. 2016;196:721–6. This SEER database review demonstrates the difficulty of having patients comply with rigerous active surveillance protocol. CrossRefPubMedGoogle Scholar
  8. 8.
    Kryvenko ON, Carter HB, Trock BJ, Epstein JI. Biopsy criteria for determining appropriateness for active surveillance in the modern era. Urology. 2014;83:869–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Mohler JL, Kantoff PW, Armstrong AJ, et al. Prostate cancer, version 1.2014. J Natl Compr Cancer Netw. 2013;11:1471–9.CrossRefGoogle Scholar
  10. 10.
    Komisarenko M, Timilshina N, Richard PO, Alibhai SMH, Hamilton R, Kulkarni G, Zlotta A, Fleshner N, Finelli A. Stricter active surveillance criteria for prostate cancer do not result in significantly better outcomes: a comparison of contemporary protocols. J Urol. 2016;196:1645–50.CrossRefPubMedGoogle Scholar
  11. 11.
    Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, Carter HB. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol. 2015;33:3379–85.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, Yamamoto T, Mamedov A, Loblaw A. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015;33:272–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Godtman RA, Holmberg E, Khatami A, Stranne J, Hugosson J. Outcome following active surveillance of men with screen-detected prostate cancer. Results from the Göteborg randomised population-based prostate cancer screening trial. Eur Urol. 2013;63:101–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Welty CJ, Cowan JE, Nguyen H, et al. Extended followup and risk factors for disease reclassification in a large active surveillance cohort for localized prostate cancer. J Urol. 2015;193:807–11.CrossRefPubMedGoogle Scholar
  15. 15.
    Selvadurai ED, Singhera M, Thomas K, Mohammed K, Woode-Amissah R, Horwich A, Huddart RA, Dearnaley DP, Parker CC. Medium-term outcomes of active surveillance for localised prostate cancer. Eur Urol. 2013;64:981–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Bokhorst LP, Valdagni R, Rannikko A, Kakehi Y, Pickles T, Bangma CH, Roobol MJ, group. for the P study. A decade of active surveillance in the PRIAS study: an update and evaluation of the criteria used to recommend a switch to active treatment. Eur Urol. 2016;70:954–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Macleod LC, Ellis WJ, Newcomb LF, et al. Timing of adverse prostate cancer reclassification on first surveillance biopsy: results from the Canary Prostate Cancer Active Surveillance Study. J Urol. 2016; doi: 10.1016/j.juro.2016.10.090.Google Scholar
  18. 18.
    Aly M, Dyrdak R, Nordström T, Jalal S, Weibull CE, Giske CG, Grönberg H. Rapid increase in multidrug-resistant enteric bacilli blood stream infection after prostate biopsy—a 10-year population-based cohort study. Prostate. 2015;75:947–56.CrossRefPubMedGoogle Scholar
  19. 19.
    Dall’Era MA, Albertsen PC, Bangma C, Carroll PR, Carter HB, Cooperberg MR, Freedland SJ, Klotz LH, Parker C, Soloway MS. Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol. 2012;62:976–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Zaytoun OM, Jones JS. Prostate cancer detection after a negative prostate biopsy: lessons learnt in the Cleveland Clinic experience. Int J Urol. 2011;18:557–68.CrossRefPubMedGoogle Scholar
  21. 21.
    Giulianelli R, Brunori S, Gentile BC, et al. Saturation biopsy technique increase the capacity to diagnose adenocarcinoma of prostate in patients with PSA< 10 ng/ml, after a first negative biopsy. Arch Ital di Urol Androl organo Uff [di] Soc Ital di Ecogr Urol e Nefrol. 2011;83:154–9.Google Scholar
  22. 22.
    Lee MC, Dong F, Stephenson AJ, Jones JS, Magi-Galluzzi C, Klein EA. The Epstein criteria predict for organ-confined but not insignificant disease and a high likelihood of cure at radical prostatectomy. Int Braz J Urol. 2011;37:123–4.CrossRefGoogle Scholar
  23. 23.
    Dinh KT, Mahal BA, Ziehr DR, et al. Incidence and predictors of upgrading and up staging among 10,000 contemporary patients with low risk prostate cancer. J Urol. 2015;194:343–9.CrossRefPubMedGoogle Scholar
  24. 24.
    • King AC, Livermore A, Laurila TAJ, Huang W, Jarrard DF. Impact of immediate TRUS rebiopsy in a patient cohort considering active surveillance for favorable risk prostate cancer. Urol Oncol Semin Orig Investig. 2013;31:739–43. This paper supports the use of an immediate, confirmatory biopsy in patients considering active surveillance, to reduce the risk of undersampling. CrossRefGoogle Scholar
  25. 25.
    Briganti A, Tutolo M, Suardi N, et al. There is no way to identify patients who will harbor small volume, unilateral prostate cancer at final pathology. Implications for focal therapies prostate. 2012;72:925–30.PubMedGoogle Scholar
  26. 26.
    Gallina A, Maccagnano C, Suardi N, et al. Unilateral positive biopsies in low risk prostate cancer patients diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate cancer at radical prostatectomy. BJU Int. 2012;110:E64–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Capitanio U, Karakiewicz PI, Valiquette L, et al. Biopsy core number represents one of foremost predictors of clinically significant Gleason sum upgrading in patients with low-risk prostate cancer. Urology. 2009;73:1087–91.CrossRefPubMedGoogle Scholar
  28. 28.
    Jones JS. Saturation biopsy for detecting and characterizing prostate cancer. BJU Int. 2007;99:1340–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Abouassaly R, Lane BR, Jones JS. Staging saturation biopsy in patients with prostate cancer on active surveillance protocol. Urology. 2008;71:573–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Thompson JE, Hayen A, Landau A, Haynes A-M, Kalapara A, Ischia J, Matthews J, Frydenberg M, Stricker PD. Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer. BJU Int. 2015;115:884–91.CrossRefPubMedGoogle Scholar
  31. 31.
    Roehl KA, Antenor JAV, Catalona WJ. Serial biopsy results in prostate cancer screening study. J Urol. 2002;167:2435–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Alberts AR, Roobol MJ, Drost F-JH, van Leenders GJ, Bokhorst LP, Bangma CH, Schoots IG. Risk-stratification based on magnetic resonance imaging and prostate-specific antigen density may reduce unnecessary follow-up biopsy procedures in men on active surveillance for low-risk prostate cancer. BJU Int. 2017; doi: 10.1111/bju.13836.Google Scholar
  33. 33.
    Patel MI, Deconcini DT, Lopez-Corona E, Ohori M, Wheeler T, Scardino PT. An analysis of men with clinically localized prostate cancer who deferred definitive therapy. J Urol. 2004;171:1520–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Adamy A, Yee DS, Matsushita K, Maschino A, Cronin A, Vickers A, Guillonneau B, Scardino PT, Eastham JA. Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer. J Urol. 2011;185:477–82.CrossRefPubMedGoogle Scholar
  35. 35.
    Cary KC, Cowan JE, Sanford M, Shinohara K, Perez N, Chan JM, Meng MV, Carroll PR. Predictors of pathologic progression on biopsy among men on active surveillance for localized prostate cancer: the value of the pattern of surveillance biopsies. Eur Urol. 2014;66:337–42.CrossRefPubMedGoogle Scholar
  36. 36.
    Tseng KS, Landis P, Epstein JI, Trock BJ, Carter HB. Risk stratification of men choosing surveillance for low risk prostate cancer. J Urol. 2010;183:1779–85.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Barayan GA, Brimo F, Bégin LR, Hanley JA, Liu Z, Kassouf W, Aprikian AG, Tanguay S. Factors influencing disease progression of prostate cancer under active surveillance: a McGill University Health Center cohort. BJU Int. 2014;114:E99–E104.CrossRefPubMedGoogle Scholar
  38. 38.
    Schiffmann J, Wenzel P, Salomon G, et al. Heterogeneity in D’Amico classification–based low-risk prostate cancer: differences in upgrading and upstaging according to active surveillance eligibility. Urol Oncol Semin Orig Investig. 2015;33:329.e13–9.CrossRefGoogle Scholar
  39. 39.
    Wang S-Y, Cowan JE, Cary KC, Chan JM, Carroll PR, Cooperberg MR. Limited ability of existing nomograms to predict outcomes in men undergoing active surveillance for prostate cancer. BJU Int. 2014;114:E18–24.CrossRefPubMedGoogle Scholar
  40. 40.
    Loeb S, Bruinsma SM, Nicholson J, Briganti A, Pickles T, Kakehi Y, Carlsson SV, Roobol MJ. Active surveillance for prostate cancer: a systematic review of clinicopathologic variables and biomarkers for risk stratification. Eur Urol. 2015;67:619–26.CrossRefPubMedGoogle Scholar
  41. 41.
    Truong M, Slezak JA, Lin CP, et al. Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer. Cancer. 2013;119:3992–4002.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    • Blute ML, Shiau JM, Truong M, Shi F, Abel EJ, Downs TM, Jarrard DF. A biopsy-integrated algorithm for determining Gleason 6 upgrading risk stratifies risk of active surveillance failure in prostate cancer. World J Urol. 2016; doi: 10.1007/s00345-016-1933-0. This article applies a biopsy-driven nomogram in predicting upgrading risk during active surveillance. PubMedGoogle Scholar
  43. 43.
    •• Iremashvili V, Manoharan M, Kava BR, Parekh DJ, Punnen S. Predictive models and risk of biopsy progression in active surveillance patients. Urol Oncol Semin Orig Investig. 2017;35:37.e1–8. This review compares various normograms and their ability to predict progression of cancer during active surveillance. CrossRefGoogle Scholar
  44. 44.
    Goode RR, Marshall SJ, Duff M, Chevli E, Chevli KK. Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy patients. Prostate. 2013;73:48–53.CrossRefPubMedGoogle Scholar
  45. 45.
    Tosoian JJ, Loeb S, Kettermann A, Landis P, Elliot DJ, Epstein JI, Partin AW, Carter HB, Sokoll LJ. Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program. J Urol. 2010;183:534–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Lin DW, Newcomb LF, Brown EC, et al. Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study. Clin Cancer Res. 2013;19:2442–50.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Berg KD, Vainer B, Thomsen FB, Røder MA, Gerds TA, Toft BG, Brasso K, Iversen P. ERG protein expression in diagnostic specimens is associated with increased risk of progression during active surveillance for prostate cancer. Eur Urol. 2014;66:851–60.CrossRefPubMedGoogle Scholar
  48. 48.
    Cuzick J, Berney DM, Fisher G, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012;106:1095–9.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Bishoff JT, Freedland SJ, Gerber L, et al. Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. J Urol. 2014;192:409–14.CrossRefPubMedGoogle Scholar
  50. 50.
    Koch MO, Cho JS, Kaimakliotis HZ, Cheng L, Sangale Z, Brawer M, Welbourn W, Reid J, Stone S. Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence. Cancer Biomarkers. 2016;17:83–8.CrossRefPubMedGoogle Scholar
  51. 51.
    Cooperberg MR, Simko JP, Cowan JE, et al. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol. 2013;31:1428–34.CrossRefPubMedGoogle Scholar
  52. 52.
    Klein EA, Cooperberg MR, Magi-Galluzzi C, et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol. 2014;66:550–60.CrossRefPubMedGoogle Scholar
  53. 53.
    Brand TC, Zhang N, Crager MR, et al. Patient-specific meta-analysis of 2 clinical validation studies to predict pathologic outcomes in prostate cancer using the 17-gene genomic prostate score. Urology. 2016;89:69–75.CrossRefPubMedGoogle Scholar
  54. 54.
    Fütterer JJ, Briganti A, De Visschere P, Emberton M, Giannarini G, Kirkham A, Taneja SS, Thoeny H, Villeirs G, Villers A. Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature. Eur Urol. 2015;68:1045–53.CrossRefPubMedGoogle Scholar
  55. 55.
    Kasel-Seibert M, Lehmann T, Aschenbach R, Guettler FV, Abubrig M, Grimm M-O, Teichgraeber U, Franiel T. Assessment of PI-RADS v2 for the detection of prostate cancer. Eur J Radiol. 2016;85:726–31.CrossRefPubMedGoogle Scholar
  56. 56.
    Rosenkrantz AB, Verma S, Choyke P, et al. Prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a prior negative biopsy: a consensus statement by AUA and SAR. J Urol. 2016;196:1613–8.CrossRefPubMedGoogle Scholar
  57. 57.
    •• Wysock JS, Rosenkrantz AB, Huang WC, Stifelman MD, Lepor H, Deng F-M, Melamed J, Taneja SS. A prospective, blinded comparison of magnetic resonance (MR) imaging–ultrasound fusion and visual estimation in the performance of MR-targeted prostate biopsy: the PROFUS trial. Eur Urol. 2014;66:343–51. This prospective, blinded study confirms that ultrasound fusion biopsies are better able to detect cancer than visual, cognitive biopsies. CrossRefPubMedGoogle Scholar
  58. 58.
    Da Rosa MR, Milot L, Sugar L, Vesprini D, Chung H, Loblaw A, Pond GR, Klotz L, Haider MA. A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance. J Magn Reson Imaging. 2015;41:220–5.CrossRefPubMedGoogle Scholar
  59. 59.
    Thompson JE, van Leeuwen PJ, Moses D, et al. The diagnostic performance of multiparametric magnetic resonance imaging to detect significant prostate cancer. J Urol. 2016;195:1428–35.CrossRefPubMedGoogle Scholar
  60. 60.
    Wysock JS, Mendhiratta N, Zattoni F, Meng X, Bjurlin M, Huang WC, Lepor H, Rosenkrantz AB, Taneja SS. Predictive value of negative 3T multiparametric magnetic resonance imaging of the prostate on 12-core biopsy results. BJU Int. 2016;118:515–20.CrossRefPubMedGoogle Scholar
  61. 61.
    Vargas HA, Hötker AM, Goldman DA, et al. Updated prostate imaging reporting and data system (PIRADS v2) recommendations for the detection of clinically significant prostate cancer using multiparametric MRI: critical evaluation using whole-mount pathology as standard of reference. Eur Radiol. 2016;26:1606–12.CrossRefPubMedGoogle Scholar
  62. 62.
    Turkbey B, Mani H, Shah V, et al. Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. J Urol. 2011;186:1818–24.CrossRefPubMedGoogle Scholar
  63. 63.
    Le JD, Tan N, Shkolyar E, Lu DY, Kwan L, Marks LS, Huang J, Margolis DJA, Raman SS, Reiter RE. Multifocality and prostate cancer detection by multiparametric magnetic resonance imaging: correlation with whole-mount histopathology. Eur Urol. 2015;67:569–76.CrossRefPubMedGoogle Scholar
  64. 64.
    Gupta RT, Faridi KF, Singh AA, Passoni NM, Garcia-Reyes K, Madden JF, Polascik TJ. Comparing 3-T multiparametric MRI and the Partin tables to predict organ-confined prostate cancer after radical prostatectomy. Urol Oncol Semin Orig Investig. 2014;32:1292–9.CrossRefGoogle Scholar
  65. 65.
    Habibian DJ, Liu CC, Dao A, Kosinski KE, Katz AE. Imaging characteristics of prostate cancer patients who discontinued active surveillance on 3-T multiparametric prostate MRI. Am J Roentgenol. 2017;208:564–9.CrossRefGoogle Scholar
  66. 66.
    Van Hemelrijck M, Garmo H, Lindhagen L, Bratt O, Stattin P, Adolfsson J. Quantifying the transition from active surveillance to watchful waiting among men with very low-risk prostate cancer. Eur Urol. 2016; doi: 10.1016/j.eururo.2016.10.031.Google Scholar
  67. 67.
    Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014;370:932–42.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    •• Droz J-P, Albrand G, Gillessen S, et al. Management of prostate cancer in elderly patients: recommendations of a task force of the International Society of Geriatric Oncology. Eur Urol. 2017; doi: 10.1016/j.eururo.2016.12.025. This article represents the latest guidelines on approaching prostate cancer treatment in the geriatric population. Google Scholar
  69. 69.
    Mottet N, Bellmunt J, Bolla M, et al. EAU–ESTRO–SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2016; doi: 10.1016/j.eururo.2016.08.003.Google Scholar
  70. 70.
    Soubeyran P, Bellera C, Goyard J, et al. Screening for vulnerability in older cancer patients: the oncodage prospective multicenter cohort study. PLoS One. 2014; doi: 10.1371/journal.pone.0115060.Google Scholar
  71. 71.
    Berger ZD, Yeh JC, Carter HB, Pollack CE. Characteristics and experiences of patients with localized prostate cancer who left an active surveillance program. Patient - Patient-Centered Outcomes Res. 2014;7:427–36.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jonathan H. Wang
    • 1
  • Tracy M. Downs
    • 1
    • 2
  • E. Jason Abel
    • 1
    • 2
  • Kyle A. Richards
    • 1
    • 2
  • David F. Jarrard
    • 1
    • 2
    • 3
  1. 1.Department of UrologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.University of Wisconsin Carbone Comprehensive Cancer CenterMadisonUSA
  3. 3.Environmental and Molecular ToxicologyUniversity of WisconsinMadisonUSA

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