PSA-IgM and iXip in the diagnosis and management of prostate cancer: clinical relevance and future potential. A review.

Main Article Content

Umberto Maestroni
Domenico Maria Cavalieri
Davide Campobasso
Giulio Guarino
Francesco Ziglioli


prostate cancer, PSA-IgM, iXip, active surveillance, immunocomplex


The Prostate Specific Antigen (PSA) is the first filter in the diagnosis of prostate cancer. Unfortunately, it is organ-specific but not cancer-specific. In addition, some prostate cancers are not clinically-significant and their diagnosis and treatment may lead to overdiagnosis and overtreatment.

For these reasons, other markers have been proposed in the last years, such as PCA3 and PHI, but none of these are currently used in the clinical practice on large scale.

In the last decade, PSA-IgM and the algorithm iXip have emerged for the diagnosis of prostate cancer and showed to perform well in decreasing the detection of clinically-insignificant prostate cancer and in reducing the number of unnecessary prostate biopsies.

This review focuses on data reported in the literature on PSA-IgM and iXip as well as on the future perspectives of their usage in the clinical practice on large scale.


Download data is not yet available.
Abstract 244 | PDF Downloads 136


1. Zitvogel L, Tesniere A, Kroemer G, Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 2006; 10: 715-27
2. Volmmers HP, Brandlein S. The “early birds”: natural IgM antibodies and immune surveillance. Histol Histopathol 2005; 20: 927-37
3. Fuchs C, Krapf F, Kern P, et al. CEA-containing immune complexes in sera of patients with colorectal and breast cancer - analysis of complexed immunoglobulin classes Cancer Immunol Immunother 1988; 26: 180-4
4. Beneduce L, Castaldi F, Marino M, et al. Squamous cell carcinoma antigen-IgM complexes as novel biomarkers for hepatocellular carcinoma. Cancer 2005; 103: 2558-65
5. Beneduce L, Prayer-Galletti T, Giustinian AMG, et al. Detection of prostate-specific antigen coupled to immunoglobulin M in prostate cancer patients. Cancer Detection and Prev 2007; 31: 402-7
6. Zhang L, Zhao F, Liang Z, et al. Effect of anti-human IgM antibody on the proliferation, apoptosis and cell cicle of Hep-2 laryngeal squamous cell carcinoma cells and potential mechanism underlying its antitumor activity. Int J Clin Exp Pthol 2017; 10: 858-68
7. Drost FH, Osses DF, Nieboer D, et al. Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst Rev 2019; 4: CD012663
doi: 10.1002/14651858.CD012663.pub2
8. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med 2018; 378: 1767-77 doi: 10.1056/NEJMoa1801993
9. Ziglioli F, Maestroni U, Manna C, et al. Multiparametric MRI in the management of prostate cancer: an update. A narrative review. Gland Surg 2020; 9: 2321-30. doi: 10.21037/gs-20-561
10. Borghesi M, Ahmed H, Nam R, et al. Complications after systematic, random and image-guided prostate biopsy. Eur Urol 2017; 71: 353-365 doi:10.1016/j.eururo.2016.08.004
11. Gallotta A, Giannarini G, Laurini L, et al. Clinical validation od the iXip index in avoiding unnecessary prostate biopsy: results from a prospective multi center study involving 426 patients. Cancer Treat and Res Comm 2017: 10: 40-45.
12. Gallotta A, Ziglioli F, Ferretti S, et al. A novel algorithm for the prediction of prostate cancer in clinically suspected patients. Cancer Biomark 2013; 13: 227-34
13. Ziglioli F, Granelli G, Cavalieri DM, et al. What chance do we have to decrease prostate cancer overdiagnosis and overtreatment? A narrative review. Acta Biomed 2019; 90:423-6 doi: 10.23750/abm.v90i4.9070
14. Galosi AB, Dell’Atti L, Bertaccini A, et al. Clinical evaluation of the iXip index to reduce prostate re-biopsies. Cancer Treat Res Commun 2018; 16: 59-63. doi: 10.1016/j.ctarc.2018.07.001
15. Lombardo R, Tema G, Cancrini F, et al. The role of immune PSA complex (iXip) in the prediction of prostate cancer. Biomarkers 2021: 26: 26-30. doi: 10.1080/1354750X.2020.1841294
16. Antonelli A, Francavilla S, Gallotta A, et al. Current evidence and future perspectives about the role of iXip in the diagnosis of prostate cancer. Minerva Urol Nefrol 2019;71:201-4. doi: 10.23736/S0393-2249.19.03329-0
17. Milanese G, Garofalo F, Mengoni P, et al. PSA-IgM based algorithm (iXip score) during follow-up of active surveillance. Anticancer Res 2017;37:2137-8
18. Bersanelli M, Gnetti L, Varotti E, et al. Immune context characterization and heterogeneity in primary tumors and pulmonary metastases from renal cell carcinoma. Immunotherapy 2019; 11: 21-35. doi: 10.2217/imt-2018-0097
19. Sutcliffe P, Hummel S, Simpson E, et al. Use of classical and novel biomarkers as prognostic risk factors for localized prostate cancer: a systematic review. Health Technol Assess 2009;13: 1-219. doi: 10.3310/hta13050
20. Freedland SJ. Screening, risk assessment, and the approach to therapy in patients with prostate cancer. Cancer 2011; 117: 1123-35. doi: 10.1002/cncr.25477
21. Na R, Ye D, Liu F, et al. Performance of serum prostate-specific antigen isoform [-2]proPSA (2pPSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population. Prostate 2014; 74: 1569-75. doi: 10.1002/pros.22876
22. Wang W, Wang M, Wang L, et al. Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis. Sci Rep 2014; 4:5012. doi: 10.1038/srep05012
23. Maestroni U, Morandin F, Ferretti S, et al. Recurrence of prostate cancer after HIFU. Proposal of a novel predictive index. Acta Biomed 2018; 89: 220-6. doi: 10.23750/abm.v89i2.6730
24. Eifler JB, Feng Z, Lin BM, et al. An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011. BJU Int 2013; 111: 22-9. doi: 10.1111/j.1464-410X.2012.11324.x
25. Tosoian JJ, Chappidi M, Feng Z, et al. Prediction of pathological stage based on clinical stage, serum prostate-specific antigen, and biopsy Gleason score: Partin Tables in the contemporary era. BJU Int 2017; 119: 676-83. doi: 10.1111/bju.13573
26. 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 2017; 71: 318-29.
27. D’Amuri FV, Maestroni U, Pagnini F, et al. Gland Surg 2019; 8: S223-32. doi: 10.21037/gs.2019.06.02

Most read articles by the same author(s)