Screening of Prostate Cancer

  • Martijn B. Busstra
  • Monique J. Roobol
Living reference work entry


In this chapter we aim to give insight in the burden of prostate cancer and the effects of early detection and treatments using ample available data from cancer registries and (randomized) clinical trials. Prostate cancer is the leading cancer type in men, and it occurs mainly at age 60–80 remaining asymptomatic during lifetime in many cases. The impact of a disease determines the need and extent of screening. Large-scale population-based prostate cancer screening trials mainly aimed to demonstrate a reduction in disease-specific mortality. After two decades it became clear that disease-specific mortality could be reduced, but at considerable harms including over diagnosis and related overtreatment. Interpretation of trial data is however hampered by, e.g., prostate-specific antigen (PSA) contamination of the control group and the continuous development of new diagnostic tools and treatment options. Nowadays, prostate cancer morbidity and quality of life are at least equally important as survival. Diagnostic strategies in prostate cancer screening protocols are now directed at trying to detect higher-risk prostate cancers in a really early phase and trying to avoid detection of low-volume, low-grade cancers. The ideal test does not (yet) exist meaning that clinically insignificant tumors will still be diagnosed and significant tumors can be missed. Until more advanced markers and diagnostic tools, less invasive treatments, and better active surveillance strategies combined into an individually tailored algorithm demonstrate a substantially better cost-effective impact, the decision whether or not to screen remains a shared decision between men and their physicians.


  1. Abdollah F, Sun M, Suardi N, Gallina A, Bianchi M, Tutolo M, Passoni N, Tian Z, Salonia A, Colombo R, Rigatti P, Karakiewicz PI, Montorsi F, Briganti A. Prediction of functional outcomes after nerve-sparing radical prostatectomy: results of conditional survival analyses. Eur Urol. 2012;62(1):42–52.CrossRefPubMedGoogle Scholar
  2. Ahmed HU, Hu Y, Carter T, Arumainayagam N, Lecornet E, Freeman A, Hawkes D, Barratt DC, Emberton M. Characterizing clinically significant prostate cancer using template prostate mapping biopsy. J Urol. 2011;186(2):458–64.CrossRefPubMedGoogle Scholar
  3. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham AP, Oldroyd R, Parker C, Emberton M, P. s. group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389:815–22.CrossRefPubMedGoogle Scholar
  4. Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, O'Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD, Team PP. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310–9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Arsov C, Becker N, Hadaschik BA, Hohenfellner M, Herkommer K, Gschwend JE, Imkamp F, Kuczyk MA, Antoch G, Kristiansen G, Siener R, Semjonow A, Hamdy FC, Lilja H, Vickers AJ, Schroder FH, Albers P. Prospective randomized evaluation of risk-adapted prostate-specific antigen screening in young men: the PROBASE trial. Eur Urol. 2013;64(6):873–5.CrossRefPubMedGoogle Scholar
  6. Bertsimas D, Silberholz J, Trikalinos T. Optimal healthcare decision making under multiple mathematical models: application in prostate cancer screening. Health Care Manag Sci. 2016.Google Scholar
  7. Bjorklund J, Folkvaljon Y, Cole A, Carlsson S, Robinson D, Loeb S, Stattin P, Akre O. Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study. BJU Int. 2016;118(2):302–6.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Black W, Ling A. Is earlier diagnosis really better? The misleading effects of lead time and length biases. AJR Am J Roentgenol. 1990;155(3):625–30.CrossRefPubMedGoogle Scholar
  9. Boehm K, Larcher A, Beyer B, Tian Z, Tilki D, Steuber T, Karakiewicz PI, Heinzer H, Graefen M, Budaus L. Identifying the most informative prediction tool for cancer-specific mortality after radical prostatectomy: comparative analysis of three commonly used preoperative prediction models. Eur Urol. 2016;69(6):1038–43.CrossRefPubMedGoogle Scholar
  10. Bokhorst LP, Kranse R, Venderbos LD, Salman JW, van Leenders GJ, Schroder FH, Bangma CH, Roobol MJ, E. R. S. Group. Differences in treatment and outcome after treatment with curative intent in the screening and control arms of the ERSPC rotterdam. Eur Urol. 2015;68(2):179–82.CrossRefPubMedGoogle Scholar
  11. Carlsson SV, Roobol MJ. Improving the evaluation and diagnosis of clinically significant prostate cancer in 2017. Curr Opin Urol. 2017;27:198–204.CrossRefPubMedGoogle Scholar
  12. Carlsson SV, de Carvalho TM, Roobol MJ, Hugosson J, Auvinen A, Kwiatkowski M, Villers A, Zappa M, Nelen V, Paez A, Eastham JA, Lilja H, de Koning HJ, Vickers AJ, Heijnsdijk EA. Estimating the harms and benefits of prostate cancer screening as used in common practice versus recommended good practice: a microsimulation screening analysis. Cancer. 2016;122(21):3386–93.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R, Fozard JL, Walsh PC. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA. 1992;267(16):2215–20.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Chodak GW, Thisted RA, Gerber GS, Johansson JE, Adolfsson J, Jones GW, Chisholm GD, Moskovitz B, Livne PM, Warner J. Results of conservative management of clinically localized prostate cancer. N Engl J Med. 1994;330(4):242–8.CrossRefPubMedGoogle Scholar
  15. Crawford ED, Higano CS, Shore ND, Hussain M, Petrylak DP. Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol. 2015;194(6):1537–47.CrossRefPubMedGoogle Scholar
  16. Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol. 2014;65(6):1058–66.CrossRefPubMedGoogle Scholar
  17. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280(11):969–74.CrossRefPubMedGoogle Scholar
  18. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R, E.-W. Group. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5 – a population-based study. Lancet Oncol. 2014;15(1):23–34.CrossRefPubMedGoogle Scholar
  19. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRefPubMedGoogle Scholar
  20. Ficarra V, Novara G, Ahlering TE, Costello A, Eastham JA, Graefen M, Guazzoni G, Menon M, Mottrie A, Patel VR, Van der Poel H, Rosen RC, Tewari AK, Wilson TG, Zattoni F, Montorsi F. Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol. 2012a;62(3):418–30.CrossRefPubMedGoogle Scholar
  21. Ficarra V, Novara G, Rosen RC, Artibani W, Carroll PR, Costello A, Menon M, Montorsi F, Patel VR, Stolzenburg JU, Van der Poel H, Wilson TG, Zattoni F, Mottrie A. Systematic review and meta-analysis of studies reporting urinary continence recovery after robot-assisted radical prostatectomy. Eur Urol. 2012b;62(3):405–17.CrossRefPubMedGoogle Scholar
  22. Fleshner K, Carlsson SV, Roobol MJ. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nat Rev Urol. 2017;14(1):26–37.CrossRefPubMedGoogle Scholar
  23. Force, U. S. P. S. T. Screening for prostate cancer: recommendation and rationale. Ann Intern Med. 2002;137(11):915–6.CrossRefGoogle Scholar
  24. Force, U. S. P. S. T. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(3):185–91.CrossRefGoogle Scholar
  25. Gaudreau PO, Stagg J, Soulieres D, Saad F. The present and future of biomarkers in prostate cancer: proteomics, genomics, and immunology advancements. Biomark Cancer. 2016;8(Suppl 2):15–33.PubMedPubMedCentralGoogle Scholar
  26. Gondos A, Krilaviciute A, Smailyte G, Ulys A, Brenner H. Cancer surveillance using registry data: results and recommendations for the Lithuanian national prostate cancer early detection programme. Eur J Cancer. 2015;51(12):1630–7.CrossRefPubMedGoogle Scholar
  27. Gronberg H, Adolfsson J, Aly M, Nordstrom T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M. Prostate cancer screening in men aged 50-69 years (STHLM3): a prospective population-based diagnostic study. Lancet Oncol. 2015;16(16):1667–76.CrossRefPubMedGoogle Scholar
  28. Guessous I, Cullati S, Fedewa SA, Burton-Jeangros C, Courvoisier DS, Manor O, Bouchardy C. Prostate cancer screening in Switzerland: 20-year trends and socioeconomic disparities. Prev Med. 2016;82:83–91.CrossRefPubMedGoogle Scholar
  29. Hendriks RJ, van Oort IM, Schalken JA. Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions. Prostate Cancer Prostatic Dis. 2017;20(1):12–9.CrossRefPubMedGoogle Scholar
  30. Hsing AW, Tsao L, Devesa SS. International trends and patterns of prostate cancer incidence and mortality. Int J Cancer. 2000;85(1):60–7.CrossRefPubMedGoogle Scholar
  31. Johansson JE, Adami HO, Andersson SO, Bergstrom R, Krusemo UB, Kraaz W. Natural history of localised prostatic cancer. A population-based study in 223 untreated patients. Lancet. 1989;1(8642):799–803.CrossRefPubMedGoogle Scholar
  32. Korfage IJ, Hak T, de Koning HJ, Essink-Bot ML. Patients’ perceptions of the side-effects of prostate cancer treatment – a qualitative interview study. Soc Sci Med. 2006;63(4):911–9.CrossRefPubMedGoogle Scholar
  33. Korfage IJ, de Koning HJ, Essink-Bot ML. Response shift due to diagnosis and primary treatment of localized prostate cancer: a then-test and a vignette study. Qual Life Res. 2007;16(10):1627–34.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kweldam CF, Kummerlin IP, Nieboer D, Verhoef EI, Steyerberg EW, van der Kwast TH, Roobol MJ, van Leenders GJ. Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy. Mod Pathol. 2016;29(6):630–6.CrossRefPubMedGoogle Scholar
  35. Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL. Latest results from the UK trials evaluating prostate cancer screening and treatment: the CAP and ProtecT studies. Eur J Cancer. 2010;46(17):3095–101.CrossRefPubMedGoogle Scholar
  36. Loeb S, Lilja H, Vickers A. Beyond prostate-specific antigen: utilizing novel strategies to screen men for prostate cancer. Curr Opin Urol. 2016;26(5):459–65.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Lu-Yao GL, Albertsen PC, Moore DF, Lin Y, DiPaola RS, Yao SL. Fifteen-year outcomes following conservative management among men aged 65 years or older with localized prostate cancer. Eur Urol. 2015;68(5):805–11.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Mohler JM. NCCN guidelines, prostate cancer version 1. 2017.Google Scholar
  39. Moyer VA, Force USPST. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(2):120–34.CrossRefPubMedGoogle Scholar
  40. Murray NP, Reyes E, Orellana N, Fuentealba C, Jacob O. Head to head comparison of the chun nomogram, percentage free PSA and primary circulating prostate cells to predict the presence of prostate cancer at repeat biopsy. Asian Pac J Cancer Prev. 2016;17(6):2941–6.PubMedGoogle Scholar
  41. Ost P, Jereczek-Fossa BA, As NV, Zilli T, Muacevic A, Olivier K, Henderson D, Casamassima F, Orecchia R, Surgo A, Brown L, Tree A, Miralbell R, De Meerleer G. Progression-free survival following stereotactic body radiotherapy for oligometastatic prostate cancer treatment-naive recurrence: a multi-institutional analysis. Eur Urol. 2016;69(1):9–12.CrossRefPubMedGoogle Scholar
  42. Popiolek M, Rider JR, Andren O, Andersson SO, Holmberg L, Adami HO, Johansson JE. Natural history of early, localized prostate cancer: a final report from three decades of follow-up. Eur Urol. 2013;63(3):428–35.CrossRefPubMedGoogle Scholar
  43. Porres D, Pfister D, Heidenreich A. Minimally invasive treatment for localized prostate cancer. Minerva Urol Nefrol. 2012;64(4):245–53.PubMedGoogle Scholar
  44. Rosenkrantz AB, Verma S, Choyke P, Eberhardt SC, Eggener SE, Gaitonde K, Haider MA, Margolis DJ, Marks LS, Pinto P, Sonn GA, Taneja SS. 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(6):1613–8.CrossRefPubMedGoogle Scholar
  45. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, Kwiatkowski M, Lujan M, Maattanen L, Lilja H, Denis LJ, Recker F, Paez A, Bangma CH, Carlsson S, Puliti D, Villers A, Rebillard X, Hakama M, Stenman UH, Kujala P, Taari K, Aus G, Huber A, van der Kwast TH, van Schaik RH, de Koning HJ, Moss SM, Auvinen A and ERSPC Investigators. 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.Google Scholar
  46. Scosyrev E, Messing EM, Mohile S, Golijanin D, Wu G. Prostate cancer in the elderly. Cancer. 2012;118(12):3062–70.CrossRefPubMedGoogle Scholar
  47. Shoag JE, Mittal S, Hu JC. Reevaluating PSA testing rates in the PLCO trial. N Engl J Med. 2016a;374(18):1795–6.CrossRefPubMedGoogle Scholar
  48. Shoag JE, Mittal S, Hu JC, et al. More on reevaluating PSA testing rates in the PLCO trial. N Engl J Med. 2016b;375(15):1500–1.CrossRefPubMedGoogle Scholar
  49. Stark JR, Perner S, Stampfer MJ, Sinnott JA, Finn S, Eisenstein AS, Ma J, Fiorentino M, Kurth T, Loda M, Giovannucci EL, Rubin MA, Mucci LA. Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J Clin Oncol. 2009;27(21):3459–64.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737–46.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Tabuchi T, Nakayama T, Fukushima W, Matsunaga I, Ohfuji S, Kondo K, Kawano E, Fukuhara H, Ito Y, Oshima A. Determinants of participation in prostate cancer screening: a simple analytical framework to account for healthy-user bias. Cancer Sci. 2015;106(1):108–14.CrossRefPubMedGoogle Scholar
  52. Tosoian JJ, Carter HB, Lepor A, Loeb S. Active surveillance for prostate cancer: current evidence and contemporary state of practice. Nat Rev Urol. 2016;13(4):205–15.CrossRefPubMedPubMedCentralGoogle Scholar
  53. van den Bos W, Muller BG, Ehdaie B, Scardino P, de la Rosette JJ. What is still needed to make focal therapy an accepted segment of standard therapy? Curr Opin Urol. 2014;24(3):247–55.CrossRefPubMedGoogle Scholar
  54. Venderbos LD. Long-term follow-up after active surveillance or curative treatment: quality of life outcomes of men with low-risk prostate cancer. Qual Life Res. 2017;26(6):1635–45.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Venderbos LD, van den Bergh RC, Roobol MJ, Schroder FH, Essink-Bot ML, Bangma CH, Steyerberg EW, Korfage IJ. A longitudinal study on the impact of active surveillance for prostate cancer on anxiety and distress levels. Psycho-Oncology. 2015;24(3):348–54.CrossRefPubMedGoogle Scholar
  56. Villa S, Kendel F, Venderbos L, Rancati T, Bangma C, Carroll P, Denis L, Klotz L, Korfage IJ, Lane AJ, Magnani T, Mastris K, Rannikko A, Roobol M, Trock B, Van den Bergh R, Van Poppel H, Valdagni R, Bellardita L. Setting an agenda for assessment of health-related quality of life among men with prostate cancer on active surveillance: a consensus paper from a European School of Oncology Task Force. Eur Urol. 2017;71(2):274–80.CrossRefPubMedGoogle Scholar
  57. Weber MF, Cunich M, Smith DP, Salkeld G, Sitas F, O'Connell D. Sociodemographic and health-related predictors of self-reported mammogram, faecal occult blood test and prostate specific antigen test use in a large Australian study. BMC Public Health. 2013;13:429.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Whiting PF, Moore TH, Jameson CM, Davies P, Rowlands MA, Burke M, Beynon R, Savovic J, Donovan JL. Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review. BJU Int. 2016;118(2):193–204.CrossRefPubMedGoogle Scholar
  59. Wolters T, Roobol MJ, van Leeuwen PJ, van den Bergh RC, Hoedemaeker RF, van Leenders GJ, Schroder FH, van der Kwast TH. A critical analysis of the tumor volume threshold for clinically insignificant prostate cancer using a data set of a randomized screening trial. J Urol. 2011;185(1):121–5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of UrologyErasmus University Medical CenterRotterdamThe Netherlands

Section editors and affiliations

  • Thomas Steuber
    • 1
  1. 1.Martini-Klinik am UKE GmbHHamburgGermany

Personalised recommendations