РСА3 – ИСТИННЫЙ ОНКОМАРКЕР РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ (ОБЗОР ЛИТЕРАТУРЫ)

Рутинное измерение уровня простатспецифического антигена (ПСА) привело к увеличению количества выполняемых биопсий предстательной железы (ПЖ). Снижение порога возрастных норм ПСА привело, в свою очередь, к увеличению числа «ненужных» биопсий ПЖ (к гипердиагностике клинически незначимого рака ПЖ (РПЖ)). В настоящее время только у 35 % пациентов с уровнем общего ПСА 4–10 нг/мл удается при биопсии выявлять РПЖ, а у 20–25 % мужчин имеет место «ПСА-негативный» РПЖ. Очевидно, что ПСА как самостоятельный маркер исчерпал свои диагностические возможности. Описанные в новейшей литературе новые онкомаркеры РПЖ, несомненно, заслуживают пристального внимания и изучения. Наиболее перспективным биомаркером из всего многообразия является РСА3.

РСА3 является лучшим предиктором РПЖ при выполнении первичной либо повторной биопсии ПЖ по сравнению с общим ПСА или другими его производными. Некоторые публикации показали возможность использования индекса РСА3 при планировании пер-вичной либо повторной биопсии ПЖ, с построением номограмм рисков, в комплексе с другими индивидуальными показателями обследования пациента, в том числе с другими новейшими биомаркерами РПЖ. Применение РСА3 в повседневной практике может способствовать увеличению специфичности диагностики РПЖ и уменьшить количество «ненужных» биопсий ПЖ.

1. Состояние онкологической помощи на-селению России в 2011 г. Под ред. В.И. Чиссова, В.В. Старинского, Г.В. Петровой М., 2012. С. 17–29.

2. Babaian R.J., Mettlin C, Kane R. The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography: findings of the American Cancer Society National Prostate Cancer Detection Project. Cancer 1992;69:1195–200.

3. Cooner W.H., Mosley B.R., Ruterford CL. et al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J Urol 1990;143(6):1146–52.

4. Лоран О.Б., Пушкарь Д.Ю., Степанов В.П., Крохотина Л.В. Дифференциальная диаг-ностика опухолей предстательной железы с помощью определения уровня простат-специфического антигена сыворотки кро-ви. М., 2000.

5. Лоран О.Б., Пушкарь Д.Ю., Франк Г.А. Простатспецифический антиген и морфо-логическая характеристика рака предста-тельной железы: Руководство для врачей. М.: МЕД-пресс, 1999.

6. Bangma C.N., Kranse R., Blijenberg B.G., Schroder F.H. The free-to-total serum prostate specific antigen ratio for staging prostatic carcinoma. J Urol 1997;157(Suppl 2): 544–7.

7. Catalona W.J. Clinical utility of measurements of free and total prostate-specific antigen (PSA). Prostate 1996; Suppl 7:64–9.

8. Seamen E., Whang M. Prostate-specific antigen density (PSAD): pole in patient evaluation and management. Urol Clin North Am 1993;20:653.

9. Cuvillier O., Malavaud B. Biomarkers of aggressiveness in prostate cancer. Prostate cancer – diagnostic and therapeutic advances. November – 2011; р. 3–20.

10. Bussemakers M.J., van Bokhoven A., Verhaegh G.W. et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999;59(23):5975–9.

11. Day J.R., Jost M., Reynolds M.A. et al. PCA3: from basic molecular science to the clinical lab. Cancer Lett 2011;301:1–6.

12. Bourdoumis A., Papatsoris A.G., Chrisofos M. et al. The novel prostate cancer antigen 3 (PCA3) biomarker. Int Braz J Urol 2010;36(6):665–8.

13. de Kok J.B., Verhaegh G.W., Roelofs R.W. et al. DD3 (PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 2002;62(9):2695–8.

14. Fradet Y., Saad F., Aprikian A. et al. uPM3, a new molecular urine test for the detection of prostate cancer. Urology 2004; 64(2):311–5.

15. Tinzl M., Marberger M., Horvath S., Chypre C. DD3 PCA3 RNA analysis in urine – a new perspective for detecting prostate cancer. Eur Urol 2004;46(2):182–6.

16. Deras I.L., Aubin S.M., Blase A. et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 2008;179(4):1587–92.

17. Groskopf J., Aubin S.M., Deras I.L. et al. APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 2006;52(6):1089–95.

18. Haese A., de la Taille A., van Poppel H. et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008;54(5):1081–8.

19. Leonard S. Marks and David G. Bostwick Prostate Cancer Specificity of PCA3 Gene Testing: Examples from Clinical Practice. Rev Urol 2008;10(3):175–81.

20. Van Gils M.P., Hessels D., van Hooij O. et al. The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; a Dutch multicenter validation of the diagnostic performance. Clin Cancer Res 2007;13(3):939–43.

21. Hessels D., Schalken J.A. The use of PCA3 in the diagnosis of prostate cancer. Nat Rev Urol 2009;6(5):255–61.

22. de la Taille A., Irani J., Graefen M. et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 2011;185(6):2119–25.

23. Hessels D., Klein Gunnewiek J.M., Oort I. et al. DD3 (PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 2003;44(1):8–15.

24. Ankerst D.P., Groskopf J., Day J.R. et al. Predicting prostate cancer risk through incorporation of prostate cancer gene 3. J Urol 2008;180:1303–8.

25. Chun F.K., de la Taille A., van Poppel H. et al. Prostate cancer gene 3 (PCA3): Development and internal validation of a novel biopsy nomogram. Eur Urol 2009;56:659–68.

26. van Gils M.P., Hessels D., Hulsbergen-van de Kaa C.A. et al. Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results. Prostate 2008;68:1215–22

27. Nakanishi H., Groskopf J., Fritsche H.A. et al. PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol 2008;179:1804–9.

28. van Poppel H., Haese A., Graefen M. et al. The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance. BJU Int 2012;109(3):360–6.

29. Auprich M., Chun F.K., Ward J.F. et al. Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging. Eur Urol 2011;59: 96–105.

30. Hessels D., van Gils M.P., van Hooij O. et al. Predicitve value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate 2010;70:10–6.

31. Ploussard G., Durand X., Xylinas E. et al. Prostate cancer antigen 3 score accurately predicts tumour volume and might help in selecting prostate cancer patients for active surveillance. Eur Urol 2011;59:422–9.

32. Pepe P., Fraggetta F., Galia A., Aragona F. Is PCA3 score useful in preoperative staging of a single microfocus of prostate cancer diagnosed at saturation biopsy? Urol Int 2012;89(2):143–7.

33. Whitman E.J., Groskopf J., Ali A. et al. PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol 2008;180:1975–8.

34. Тosoian J.J., Loeb S., Kettermann A. et al. Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program. J Urol 2010;183:534–8.

35. Crawford E.D., Rove K.O., Trabulsi E.J. et al. Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: A prospective study of 1,962 cases. J Urol 2012;188:1726–31.

36. Ochiai A., Okihara K., Kamoi K. et al. Prostate cancer gene 3 urine assay for prostate cancer in Japanese men undergoing prostate biopsy. Int J Urol 2011;18:200–5. 37. Salagierski M., Mulders P., Schalken J.A. Predicting prostate biopsy outcome using a PCA3-based nomogram in a Polish cohort. Anticancer Res 2013;33:553–7.

37. Auprich M., Haese A., Walz J. et al. External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome. Eur Urol 2010;8:727–32.

38. Wu A.K., Reese A.C., Cooperberg M.R. et al. Utility of PCA3 in patients undergoing repeat biopsy for prostate cancer. Prostate Cancer Prostatic Dis 2012;15:100–5.

39. Hansen J., Auprich M., Ahyai S.A. et al. Initial prostate biopsy: Development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay. Eur Urol 2013;63:201–9.

40. Ruffion A., Devonec M., Champetier D. et al. PCA3 and PCA3-based nomograms improve diagnostic accuracy in patients undergoing first prostate biopsy. Int J Mol Sci 2013;14(9):17767–80.

41. Galasso F., Giannella R., Bruni P. еt al. PCA3: a new tool to diagnose prostate cancer (PCa) and a guidance in biopsy decisions. Preliminary report of the UrOP study. Arch Ital Urol Androl 2010;82(1):5–9.

42. Gittelman M.C., Hertzman B., Bailen J. еt al. PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol 2013;190(1):64–9.

43. Pepe P., Aragona F. PCA3 score vs PSA free/total accuracy in prostate cancer diagnosis at repeat saturation biopsy. Anticancer Res 2011;31(12):4445–9.

44. Кишкун А.А. Клиническая лаборатор-ная диагностика: учебное пособие. М., 2010. С. 32–33.

45. De Koning H.J., Essink-Bot M.L., Schroder F.H. Screening for prostate cancer. In: Prostate cancer. Clinical and scientific aspects – bridging the gap. P.D. Abel, E.-N. Lafani (eds.). London, United Kingdom: Imperial College Press, 2003. P. 683–708.

46. Roddam A.W., Hamdy F.C., Allen N.E., Price C.P. The impact of reducing the prostate-specific antigen threshold and including isoform reflex tests on the performance characteristics of a prostate-cancer detection programme. BJU Int 2007;100:514–7.

47. Leitenberger A., Altwein J.E. Efficacy and discriminative ability of prostate-specific antigen as a tumor marker. Eur Urol 1990;17(1):12–6.

48. Mettlin C., Lee F., Drago J., Murphy G.P. The American Cancer Society National Prostate Cancer Detection Project. Findings on the detection of early prostate cancer in 2425 men. Cancer 1991;67(12):2949–58.

49. Teillac P., Bron J., Tobolski F. et al. Detection of cancer of the prostate. A study of 600 cases. Ann Urol (Paris) 1990;24(1):37–41.

50. Schilling D., Hennenlotter J., Munz M. et al. Interpretation of the prostate cancer gene 3 in reference to the individual clinical background: implications for daily practice. Urol Int 2010;85(2):159–65.

51. Hammerer P., Huland H. Systemic sextant biopsies in 651 patients referred for prostate evaluation. J Urol 1994;151:99–102.

52. Hodge K.K., McNeal J.E., Terris M.K. et al. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 1989;142:71–5.

53. Livene M.A., Ittman M., Melamed J. et al. Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate on predicting Gleason score of prostate cancer. J Urol 1998;159:471–6.

54. Svetec D., McCabe K., Peretsman S. et al. Prostate rebiopsy is a poor surrogate of treat-ment efficacy in localized prostate cancer. J Urol 1998;159:1606–8.

55. Говоров А.В. Оптимизация трансрек-тальной биопсии простаты в диагностике рака предстательной железы. Автореф. дис. ... канд. мед. наук. М., 2002.

56. Guichard G., Larrй S., Gallina A. et al. Extended 21-sample needle biopsy protocol for diagnosis of prostate cancer in 1000 consecutive patients. Eur Urol 2007;52:430–5.

57. Applewhite J.C., Matlaga B.R., McCullough D.L. Results of the 5 region prostate biopsy method: the repeat biopsy population. J Urol 2002;168:500–3.

58. Djavan B., Ravery V., Zlotta A. et al. Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J Urol 2001;166:1679–83.

59. Marks L.S., Fradet Y., Deras I.L. et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology 2007;69:532–5.

60. Aubin S.M., Reid J., Sarno M.J. et al. PCA3 molecular urine test for predicting repeat prostate biopsy outcome in populations at risk: validation in the placebo arm of the dutasteride REDUCE trial. J Urol 2010;184:1947–52.62. Adam A., Engelbrecht M.J., Bornman M.S. et al. The role of the PCA3 assay in predicting prostate biopsy outcome in a South African setting. BJU Int 2011;108:1728–33.

61. Clarke R.A., Zhao Z., Guo A.Y. et al. New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression. PLoS One 2009;4(3):4995.

62. Laxman B., Morris D.S., Yu J. et al. A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res 2008;68:645–9.

63. Ouyang B., Bracken B., Burke B. et al. A duplex quantitative polymerase chain reaction assay based on quantification of alpha-methylacyl-CoA racemase transcripts and prostate cancer antigen 3 in urine sediments improved diagnostic accuracy for prostate cancer. J Urol 2009;181:2508–13.

64. Stephan C., Jung K., Semjonow A. et al. Comparative assessment of urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion with the serum [-2]proprostate-specific antigen-based prostate health index for detection of prostate cancer. Clin Chem 2013;59(1):280–8.

65. Robert G., Jannink S., Smit F. et al. Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis. Prostate 2013;73(2):113–20.