What Are Some New Developments in Prostate Cancer Diagnosis?

Article information

J Korean Med Assoc. 2010;53(2):107-118
Publication date (electronic) : 2010 February 28
doi : https://doi.org/10.5124/jkma.2010.53.2.107
Department of Urology, Sungkyunkwan University School of Medicine, Korea. besthml@medimail.co.kr

Abstract

The purpose of this article is to summarize up-to-date changes and policies in the diagnosis of prostate cancer. The triads of DRE (digital rectal examination), serum PSA (prostate specific antigen), and TRUS (transrectal ultrasound) that directed prostatic biopsy have been considered a gold standard in the early detection of prostate cancer. Even though PSA is a very useful test, its low specificity has made some controversy until now. Moreover, it is not verified whether PSA screening would contribute to the decline in prostate cancer mortality. TRUS directed prostate biopsy also has some criticisms. For example, appropriate number of biopsy core, determination of whether a patient should undergo a repeat biopsy and its timing remain controversial. This article presents guidelines on prostate cancer diagnosis with partial results of randomized controlled trials to verify aforementioned criticisms Since recently published trials show different results regarding the impact of prostate cancer screening on mortality, further analyses are needed to determine the specific parameters for optimal screening (i.e. the age at which screening should begin, re-screening intervals, the age at which screening should be discontinued, and novel screening biomarkers). Unless a new and effective screening biomarker is discovered, PSA will maintain a superlative position for screening of prostate cancer. Hence, we have to find an optimal cut-off value of PSA derivatives for Korean people. With respect to prostate biopsy, current literatures support the use of more extensive biopsy techniques to increase the likelihood of prostate cancer detection.

References

1. National Cancer Institute Surveillance epidemiology and End Results Program. Cancer statistics review-Browse the Tables and Figures-Prostate annual incidence rate 4 December 2009. Accessed at http://seer.cancer.gov/csr/1975_2006/browse_csr.php.
2. Korean National Statistical Office. The incidence of cancer statistics, 2002-2005 2005. Seoul: Korean National Statistical Office;
3. Sim HG, Cheng CW. Changing demography of prostate cancer in Asia. Eur J Cancer 2005. 41834–845.
4. Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of a human prostate specific antigen. Invest Urol 1979. 17159–163.
5. Potosky AL, Miller BA, Albertsen PC, Kramer BS. The role of increasing detection in the rising incidence of prostate cancer. Jama 1995. 273548–552.
6. Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects. CA Cancer J Clin 2007. 5790–104.
7. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 2001. 58843–848.
8. Nielsen C, Lang RS. Principles of screening. Med Clin North Am 1999. 831323–1337. v.
9. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Maattanen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009. 3601320–1328.
10. Draisma G, Boer R, Otto SJ, van der Cruijsen IW, Damhuis RA, Schroder FH, de Koning HJ. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst 2003. 95868–878.
11. 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. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009. 3601310–1319.
12. Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Haggman M, Andersson SO, Spangberg A, Busch C, Nordling S, Palmgren J, Adami HO, Johansson JE, Norlen BJ. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 2002. 347781–789.
13. Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, Kuban DA, Sartor AO, Stanford JL, Zietman A, Carroll P. Prostate specific antigen best practice statement: 2009 update. J Urol 2009. 1822232–2241.
14. Loeb S, Roehl KA, Antenor JA, Catalona WJ, Suarez BK, Nadler RB. Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old. Urology 2006. 67316–320.
15. Antenor JA, Han M, Roehl KA, Nadler RB, Catalona WJ. Relationship between initial prostate specific antigen level and subsequent prostate cancer detection in a longitudinal screening study. J Urol 2004. 17290–93.
16. Ross KS, Carter HB, Pearson JD, Guess HA. Comparative efficiency of prostate-specific antigen screening strategies for prostate cancer detection. Jama 2000. 2841399–1405.
17. Carter HB, Epstein JI, Partin AW. Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease. Urology 1999. 53126–130.
18. Smith CV, Bauer JJ, Connelly RR, Seay T, Kane C, Foley J, Thrasher JB, Kusuda L, Moul JW. Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database. J Urol 2000. 1641964–1967.
19. Thompson IM, Tangen CM, Goodman PJ, Lucia MS, Klein EA. Chemoprevention of prostate cancer. J Urol 2009. 182499–507. discussion 8.
20. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med 2004. 3502239–2246.
21. Catalona WJ, Ramos CG, Carvalhal GF, Yan Y. Lowering PSA cutoffs to enhance detection of curable prostate cancer. Urology 2000. 55791–795.
22. Schroder FH, van der Cruijsen-Koeter I, de Koning HJ, Vis AN, Hoedemaeker RF, Kranse R. Prostate cancer detection at low prostate specific antigen. J Urol 2000. 163806–812.
23. Punglia RS, D'Amico AV, Catalona WJ, Roehl KA, Kuntz KM. Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen. N Engl J Med 2003. 349335–342.
24. Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med 2008. 149192–199.
25. Choi YD, Kang DR, Nam CM, Kim YS, Cho SY, Kim SJ, Cho IR, Cho JS, Hong SJ, Ham WS. Age-specific prostate-specific antigen reference ranges in Korean men. Urology 2007. 701113–1116.
26. Cho JS, Kim SI, Kim SJ, Kim YS, Kim CI, Kim HS, Hong SJ. Lowering prostate-specific antigen threshold for prostate biopsy in Korean men: Impact on the number needing biopsy. Korean J Urol 2007. 49118–121.
27. Oesterling JE. Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol 1991. 145907–923.
28. Klein LT, Lowe FC. The effects of prostatic manipulation on prostate-specific antigen levels. Urol Clin North Am 1997. 24293–297.
29. Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS, et al. The Finasteride Study Group. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med 1992. 3271185–1191.
30. Tzanakis I, Kazoulis S, Girousis N, Kagia S, Spandidakis V, Karefillakis N, Georgila M, Cristoulakis I, Hatzilias P, Kallivretakis N. Prostate-specific antigen in hemodialysis patients and the influence of dialysis in its levels. Nephron 2002. 90230–233.
31. Slev PR, La'ulu SL, Roberts WL. Intermethod differences in results for total PSA, free PSA, and percentage of free PSA. Am J Clin Pathol 2008. 129952–958.
32. 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. 2672215–2220.
33. Roobol MJ, Kranse R, de Koning HJ, Schroder FH. Prostate-specific antigen velocity at low prostate-specific antigen levels as screening tool for prostate cancer: results of second screening round of ERSPC (ROTTERDAM). Urology 2004. 63309–313. discussion 13-15.
34. Fang J, Metter EJ, Landis P, Carter HB. PSA velocity for assessing prostate cancer risk in men with PSA levels between 2.0 and 4.0 ng/ml. Urology 2002. 59889–893. discussion 93-94.
35. Moul JW, Sun L, Hotaling JM, Fitzsimons NJ, Polascik TJ, Robertson CN, Dahm P, Anscher MS, Mouraviev V, Pappas PA, Albala DM. Age adjusted prostate specific antigen and prostate specific antigen velocity cut points in prostate cancer screening. J Urol 2007. 177499–503. discussion-4.
36. Carter HB, Ferrucci L, Kettermann A, Landis P, Wright EJ, Epstein JI, Trock BJ, Metter EJ. Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. J Natl Cancer Inst 2006. 981521–1527.
37. D'Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004. 351125–135.
38. Vickers AJ, Savage C, O'Brien MF, Lilja H. Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol 2009. 27398–403.
39. Benson MC, Whang IS, Pantuck A, Ring K, Kaplan SA, Olsson CA, Cooner WH. Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. J Urol 1992. 147815–816.
40. Seaman E, Whang M, Olsson CA, Katz A, Cooner WH, Benson MC. PSA density (PSAD). Role in patient evaluation and management. Urol Clin North Am 1993. 20653–663.
41. Djavan B, Zlotta AR, Remzi M, Ghawidel K, Bursa B, Hruby S, Wolfram R, Schulman CC, Marberger M. 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. 54846–852.
42. Singh H, Canto EI, Shariat SF, Kadmon D, Miles BJ, Wheeler TM, Slawin KM. Predictors of prostate cancer after initial negative systematic 12 core biopsy. J Urol 2004. 1711850–1854.
43. Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ, Panser LA, Lieber MM. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. Jama 1993. 270860–864.
44. Dalkin BL, Ahmann FR, Kopp JB. Prostate specific antigen levels in men older than 50 years without clinical evidence of prostatic carcinoma. J Urol 1993. 1501837–1839.
45. Partin AW, Criley SR, Subong EN, Zincke H, Walsh PC, Oesterling JE. Standard versus age-specific prostate specific antigen reference ranges among men with clinically localized prostate cancer: A pathological analysis. J Urol 1996. 1551336–1339.
46. Reed A, Ankerst DP, Pollock BH, Thompson IM, Parekh DJ. Current age and race adjusted prostate specific antigen threshold values delay diagnosis of high grade prostate cancer. J Urol 2007. 1781929–1932. discussion 32.
47. Christensson A, Bjork T, Nilsson O, Dahlen U, Matikainen MT, Cockett AT, Abrahamsson PA, Lilja H. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol 1993. 150100–105.
48. Lilja H. Significance of different molecular forms of serum PSA. The free, noncomplexed form of PSA versus that complexed to alpha 1-antichymotrypsin. Urol Clin North Am 1993. 20681–686.
49. Stenman UH, Hakama M, Knekt P, Aromaa A, Teppo L, Leinonen J. Serum concentrations of prostate specific antigen and its complex with alpha 1-antichymotrypsin before diagnosis of prostate cancer. Lancet 1994. 3441594–1598.
50. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, Richie JP, deKernion JB, Walsh PC, Scardino PT, Lange PH, Subong EN, Parson RE, Gasior GH, Loveland KG, Southwick PC. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. Jama 1998. 2791542–1547.
51. Catalona WJ, Smith DS, Wolfert RL, Wang TJ, Rittenhouse HG, Ratliff TL, Nadler RB. Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening. Jama 1995. 2741214–1220.
52. Roehl KA, Antenor JA, Catalona WJ. Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range. J Urol 2002. 168922–925.
53. Raaijmakers R, Blijenberg BG, Finlay JA, Rittenhouse HG, Wildhagen MF, Roobol MJ, Schroder FH. Prostate cancer detection in the prostate specific antigen range of 2.0 to 3.9 ng/ml: value of percent free prostate specific antigen on tumor detection and tumor aggressiveness. J Urol 2004. 1712245–2249.
54. Parsons JK, Brawer MK, Cheli CD, Partin AW, Djavan R. Complexed prostate specific antigen (PSA) reduces unnecessary prostate biopsies in the 2.6-4.0 ng/mL range of total PSA. BJU Int 2004. 9447–50.
55. Kirby RS, Fitzpatrick JM, Irani J. Prostate cancer diagnosis in the new millennium: strengths and weaknesses of prostate-specific antigen and the discovery and clinical evaluation of prostate cancer gene 3 (PCA3). BJU Int 2009. 103441–445.
56. Paul B, Dhir R, Landsittel D, Hitchens MR, Getzenberg RH. Detection of prostate cancer with a blood-based assay for early prostate cancer antigen. Cancer Res 2005. 654097–4100.
57. Schmid HP, Riesen W, Prikler L. Update on screening for prostate cancer with prostate-specific antigen. Crit Rev Oncol Hematol 2004. 5071–78.
58. Gosselaar C, Roobol MJ, van den Bergh RC, Wolters T, Schroder FH. Digital Rectal Examination and the Diagnosis of Prostate Cancer-a Study Based on 8 Years and Three Screenings within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam. Eur Urol 2009. 55139–147.
59. Cirillo S, Petracchini M, Della Monica P, Gallo T, Tartaglia V, Vestita E, Ferrando U, Regge D. Value of endorectal MRI and MRS in patients with elevated prostate-specific antigen levels and previous negative biopsies to localize peripheral zone tumours. Clin Radiol 2008. 63871–879.
60. Lawrentschuk N, Fleshner N. The role of magnetic resonance imaging in targeting prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen levels. BJU Int 2009. 103730–733.
61. Pallwein L, Mitterberger M, Pelzer A, Bartsch G, Strasser H, Pinggera GM, Aigner F, Gradl J, Zur Nedden D, Frauscher F. Ultrasound of prostate cancer: recent advances. Eur Radiol 2008. 18707–715.
62. Sen J, Choudhary L, Marwah S, Godara R, Marwah N, Sen R. Role of colour Doppler imaging in detecting prostate cancer. Asian J Surg 2008. 3116–19.
63. Prostate cancer early detection. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2004. 2190–207.
64. Presti JC Jr, Chang JJ, Bhargava V, Shinohara K. The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial. J Urol 2000. 163163–166. discussion 6-7.
65. Presti JC Jr, O'Dowd GJ, Miller MC, Mattu R, Veltri RW. 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. 169125–129.
66. Guichard G, Larre S, Gallina A, Lazar A, Faucon H, Chemama S, Allory Y, Patard JJ, Vordos D, Hoznek A, Yiou R, Salomon L, Abbou CC, de la Taille A. Extended 21-sample needle biopsy protocol for diagnosis of prostate cancer in 1000 consecutive patients. Eur Urol 2007. 52430–435.
67. Djavan B, Zlotta AR, Ekane S, Remzi M, Kramer G, Roumeguere T, Etemad M, Wolfram R, Schulman CC, Marberger M. Is one set of sextant biopsies enough to rule out prostate Cancer? Influence of transition and total prostate volumes on prostate cancer yield. Eur Urol 2000. 38218–224.
68. Djavan B, Mazal P, Zlotta A, Wammack R, Ravery V, Remzi M, Susani M, Borkowski A, Hruby S, Boccon-Gibod L, Schulman CC, Marberger M. Pathological features of prostate cancer detected on initial and repeat prostate biopsy: results of the prospective European Prostate Cancer Detection study. Prostate 2001. 47111–117.
69. Djavan B, Ravery V, Zlotta A, Dobronski P, Dobrovits M, Fakhari M, Seitz C, Susani M, Borkowski A, Boccon-Gibod L, Schulman CC, Marberger M. Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J Urol 2001. 1661679–1683.
70. Roehl KA, Antenor JA, Catalona WJ. Serial biopsy results in prostate cancer screening study. J Urol 2002. 1672435–2439.
71. Moore CK, Karikehalli S, Nazeer T, Fisher HA, Kaufman RP Jr, Mian BM. Prognostic significance of high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation in the contemporary era. J Urol 2005. 17370–72.
72. Mian BM, Naya Y, Okihara K, Vakar-Lopez F, Troncoso P, Babaian RJ. Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy. Urology 2002. 60836–840.
73. Herawi M, Kahane H, Cavallo C, Epstein JI. Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of high grade prostatic intraepithelial neoplasia is related to the number of cores sampled. J Urol 2006. 175121–124.
74. Oesterling JE, Kumamoto Y, Tsukamoto T, Girman CJ, Guess HA, Masumori N, Jacobsen SJ, Lieber MM. Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men. Br J Urol 1995. 75347–353.
75. He D, Wang M, Chen X, Gao Z, He H, Zhau HE, Wang W, Chung LW, Nan X. Ethnic differences in distribution of serum prostate-specific antigen: a study in a healthy Chinese male population. Urology 2004. 63722–726.

Article information Continued

Figure 1

The cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; p=0.04). (Schroder, et al.(9) reproduced with permission of the publisher, NEJM).

Figure 2

Number of prostate cancer deaths. Through 10 years, there was little difference between the two groups in terms of the proportion of deaths according to tumor stage. (Andriole, et al.(11) reproduced with permission of the publisher, NEJM).

Table 1

Up- to-date guidelines on prostate cancer screening

Table 1

*AUA 2009 refer to the AUA Best Practice Statement 2009

PSA: prostate-specific antigen, PSAV: PSA velocity, DRE: digital rectal examination, AUA: American Urologic Association, EAU: European Urology, NCCN: National Comprehensive Cancer Network, ACS : American Cancer Society, USPSTF: United States Preventive Services Task Force

Table 2

Comparisons of age-specific PSA reference ranges in each country

Table 2

PSA: prostate-specific antigen

Table 3

Prostate biopsy indications

Table 3

PSA: prostate-specific antigen, PSAV: PSA velocity, DRE: digital rectal examination, ASAP: aty-pical small acinar proliferation, PIN: prostate intraepithelial neoplasia