Диагностическая значимость [-2]proPSA и PHI (обзор литературы)

Измерение уровня простат-специфического антигена (ПСА) в крови привело к увеличению количества выполняемых биопсий предстательной железы (ПЖ), а снижение порога возрастных норм ПСА – к увеличению числа «ненужных» биопсий ПЖ. Сегодня только у 35 % пациентов с уровнем общего ПСА 4–10 нг / мл выявляется рак предстательной железы (РПЖ), а у 20–25 % имеет место «ПСА-негативный» РПЖ. Очевидно, ПСА, как самостоятельный маркер, исчерпал свои диагностические возможности. Представленные в литературе новые маркеры РПЖ, несомненно, заслуживают пристального внимания и изучения. К наиболее перспективным маркерам относятся также [-2]proPSA и PHI (Prostate Health Index, индекс здоровья ПЖ). Согласно последним данным литературы в настоящее время [-2]proPSA и PHI являются лучшими предикторами РПЖ при выполнении как первичной, так и повторной биопсии ПЖ. В некоторых публикациях показана возможность использования PHI при планировании и первичной, и повторной биопсии ПЖ, с построением номограмм рисков, в комплексе с другими индивидуальными показателями обследования пациента, в том числе с другими новейшими биомаркерами РПЖ. Применение [-2]proPSA и PHI в повседневной практике может способствовать увеличению специфичности диагностики РПЖ и уменьшению количества «ненужных» биопсий ПЖ. Очевидная важность диагностики РПЖ на ранних стадиях (в том числе с использованием PHI) побудила нас провести собственное исследование по данной теме. Несмотря на значительное число печатных работ, посвященных данной проблеме, их количество продолжает увеличиваться, но четкие руководства к действию в этой области пока не разработаны, и решение по каждому конкретному случаю принимается индивидуально.

1. Ferlay J., Autier P., Boniol M. et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18(3):581–92.

2. Siegel R., DeSantis C., Virgo K. et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 2012;62(4):220–41.

3. Parkin D.M., Bray F.I., Devesa S.S. Cancer burden in the year 2000: the global picture. Eur J Cancer 2001;37:4–66.

4. Cancer incidence in Sweden 2004. The National Board of Health and Welfare: Stockholm. http://sjp.sagepub.com/cgi/reprint/34/67_suppl/3.pdf.

5. Schroder F.H., Hugosson J., Roobol M.J. et al. Screening and prostate cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–28.

6. Andriole G.L., Crawford E.D., Grubb R.L. et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310–19.

7. Noldus J., Graefen M., Haese A. et al. Stage migration in clinically localized prostate cancer. Eur Urol 2000; 38; 74–78.

8. Лоран О.Б., Пушкарь Д.Ю., Степанов В.П., Крохотина Л.В. Дифференциальная диагностика опухолей предстательной железы с помощью определения уровня простатспецифического антигена сыворотки крови. М., 2000.

9. Лоран О.Б., Пушкарь Д.Ю., Франк Г.А. Простатспецифический антиген и морфологическая характеристика рака предстательной железы: Руководство для врачей. М.: МЕДпресс, 1999.

10. 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 Urology 1997;157: 544–7.

11. Catalona W.J. Clinical utility of measurements of free and total prostatespecific antigen (PSA). Prostate 1996; : 64–9.

12. Seamen E., Whang M. Prostate-specific antigen3 density (PSAD): pole in patient evaluation and management. Urol Clin North Am 1993;20:653–6.

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

14. Пушкарь Д.Ю., Говоров А.В. Маркеры рака предстательной железы. Экспериментальная и клиническая урология 2001; 2–3:19–21.

15. Mikolajczyk S.D., Marker K.M., Millar L.S. et al. A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res 2001;61:6958–63.

16. Peter J., Unverzagt C., Krogh T.N. et al. Identification of precursor forms of prostatespecific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry. Cancer Res 2001;61:957–62.

17. Mikolajczyk S.D., Marks L.S., Partin A.W., Rittenhouse H.G. Free prostate-specific antigen in serum is becoming more complex. Urology 2002;59:797–802.

18. Chen Z., Chen H., Stamey T.A. Prostate specific antigen in benign prostatic hyperplasia: purification and characterization. J Urol 1997;157:2166–70.

19. Zhang W.M., Leinonen J., Kalkkinen N. et al. Purification and characterization of different molecular forms of prostatespecific antigen in human seminal fluid. Clin Chem 1995;41:1567–73.

20. Mikolajczyk S.D., Grauer L.S., Millar L.S. et al. A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology 1997;50:710–4.

21. Mikolajczyk S.D., Millar L.S., Wang T.J. et al. “BPSA,” a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia. Urology 2000;55:41–5.

22. Mikolajczyk S.D., Rittenhouse H.G. Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer. Keio J Med 2003;52:86–91.

23. Makarov D., Isharwal S., Sokoll L. et al. Pro-prostate-specific antigen мeasurements in serum and biopsy tissue predict the need for prostate cancer treatment among men enrolled in an expectant management program. Clin Cancer Res 2009;15:7316–21.

24. Hori S., Blanchet J.S., McLoughlin J. From prostate-specific antigen (PSA) to precursor PSA (proPSA) isoforms: a review of the emerging role of proPSA in the detection and management of early prostate cancer. BJU International 2013;112:6.

25. Sokoll L.J., Chan D.W., Mikolajczyk S.D. et al. Proenzyme psa for the early detection of prostate cancer in the 2.5–4.0 ng/ml total psa range: preliminary analysis. Urology 2003;61:274–6.

26. Khan M.A., Partin A.W., Rittenhouse H.G. et al. Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml. J Urol 2003;170:723–6.

27. Sokoll L.J., Wang Y., Feng Z. et al. [-2] proenzyme prostate specific antigen for prostate cancer detection: a national cancer institute early detection research network validation study. J Urol 2008;180:539–43.

28. Catalona W.J., Bartsch G., Rittenhouse H.G. et al. Serum pro-prostate specific antigen cancers in men with 2 to 4 ng/ml prostate specific antigen. J Urol 2004;171:2239–44.

29. Stephan C., Kahrs A.M., Cammann H. et al. A [-2]proPSA-based artificial neural network significantly improves differentiation between prostate cancer and benign prostatic diseases. Prostate 2009;69(2):198–207.

30. Le B.V., Griffin C.R., Loeb S. et al. [-2] Proenzyme prostate specific antigen is more accurate than total and free prostate specific antigen in differentiating prostate cancer from benign disease in a prospective prostate cancer screening study. J Urol 2010;183(4):1355–9.

31. Catalona W.J., Partin A.W., Sanda M.G. et al. A Multicenter study of [–2]Pro-Prostate- Specific Antigen (PSA) in combination with PSA and free PSA for prostate cancer detection in the 2.0 to 10.0 ng/mL PSA range. J Urol 2011;185:1650–5.

32. Jansen F.H., van Schaik R.H., Kurstjens J. et al. Prostate-specific antigen (PSA) isoform p2PSA in combination with total PSA and free PSA improves diagnostic accuracy in prostate cancer detection. Eur Urol 2010;57(6):921–7.

33. Guazzoni G., Nava L., Lazzeri M. et al. Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting. Eur Urol 2011; 60(2):214–22.

34. Lazzeri M., Haese A., Abrate A. et al. Clinical performance of serum prostatespecific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project. BJU Int 2013;112(3):313–21.

35. Catalona W.J., Bartsch G., Rettenhous H.G. Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml. J Urol 2003;170:2181–5.

36. Khan M.A., Sokoll L.J., Chan D.W. еt al. Clinical utility of proPSA and "benign" PSA when percent free PSA is less than 15%. Urology. 2004;64(6):1160–4.

37. Sokoll L.J., Sanda M.G., Feng Z. et al. A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [-2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol Biomarkers Prev 2010;19:1193–200.

38. Vincendeau S., Ramirez J. The beckman coulter prostate health index (phi) improves diagnostic accuracy in prostate cancer detection. Eur Urol Suppl 2010;9:309.

39. Guazonni G., Lazzeri M., Nava L. et al. Preoperative prostate-specific antigen isoform p2PSA and its derivates, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer. Eur Urol 2012;61:455–66.

40. Filella X., Giménez N. Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis. Clin Chem Lab Med 2013;51(4):729–39.

41. Houlgatte A., Vincendeau S., Desfemmes F. et al. [Use of [-2] pro PSA and phi index for early detection of prostate cancer: a prospective of 452 patients]. Prog Urol 2012;22(5):279–83.

42. Lughezzani G., Lazzeri M., Larcher A. et al. Development and internal validation of a Prostate Health Index based nomogram for predicting prostate cancer at extended biopsy. J Urol 2012;188:1144–50.

43. Lazzeri M., Briganti A., Scattoni V. et al. Serum index test %[-2]proPSA and Prostate Health Index are more accurate than prostate specific antigen and %fPSA in predicting a positive repeat prostate biopsy. J Urol 2012; 88(4):1137–4.

44. Lazzeri M., Haese A., de la Taille A. et al. Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study. Eur Urol 2013; 63(6): 986–94.

45. Roobol M.J., Semjonow A., Bangma C.H. Performance of the ERSPC risk calculator for high grade prostate cancer in a clinical setting and the additional value of the Prostate Health Index (PHI®). J Urol Suppl 2011:139.

46. Carter H.B., Walsh P.C., Landis P., Epstein J.I. Expectant management of nonpalpable prostate cancer with curative intent: preliminary results. J Urol 2002;167:1231–4.

47. Tosoian J.J., Trock B.J., Landis P. et al. Active surveillance program for prostate cancer: an update of the Johns Hopkins experience. J Clin Oncol 2011;29:2185.

48. Epstein J.I., Walsh P.C., Carmichael M. Brendler C.B. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994;271:368–74.

49. Mohler J., Bahnson R.R., Boston B. et al. NCCN clinical practice guidelines in oncology: prostate cancer. J Natl Compr Canc Netw 2010;8:162–200.

50. Tosoian J.J., Loeb S., Feng Z. et al. Association of [–2]proPSA with Biopsy Reclassification During Active Surveillance for Prostate Cancer. J Urol 2012;188: 1131–6.