What chance do we have to decrease prostate cancer overdiagnosis and overtreatment? A narrative review

What chance do we have to decrease prostate cancer overdiagnosis and overtreatment? A narrative review


  • Francesco Ziglioli Department of Urology, University-Hospital of Parma, Italy
  • Giorgia Granelli Department of Urology, University-Hospital of Parma, Italy
  • Domenico Cavalieri Department of Urology, University-Hospital of Parma, Italy
  • Tommaso Bocchialini Department of Urology, University-Hospital of Parma, Italy
  • Umberto Maestroni Department of Urology, University-Hospital of Parma, Italy


Prostate cancer, PSA-IgM, iXip, PCA3, PHI Index, Targeted biopsy, Overtreatment


In the era of biochemical tests and algorithms, the management of prostate cancer from prevention to treatment is still controversial. The debate is focused on clinically-significant and clinically-insignificant prostate cancer. As it is well known, the diagnostic tools available are not able to distinguish between the two, thus leading to men treated for prostate cancer even if not strictly necessary. Unfortunately, as of today, there is no test available able to predict the clinical aggressiveness of prostate cancer at the time of the diagnosis. However, some indexes, PSA derivatives, immunocomplexes, and diagnostic methods have been proposed. If properly used in the daily clinical practice, these tools may be of support in the decision making process, in the effort to reduce the overdiagnosis and the overtreatment of prostate cancer.For this reason, we believe that a clear knowledge of this tools, indexes and diagnostic methods is of the utmost importance in preventing the morbidities related to unnecessary treatment as weel as preventing the detrimental effect of missing the diagnosis of a clinically significant prostate cancer.This reviews encompasses the most studied tests and diagnostic methods to predict the aggressiveness of prostate cancer, to avoid to miss a diagnosis of clinically significant cancers and to optimize the overall pre-treatment work-up. (www.actabiomedica.it)


1. Andriole GL, Crawford ED, Grubb RL 3rd, et al. Mortality results from a randomized prostate cancer screening trial. N Engl J Med 2009; 360: 1310-9
2. Shröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality in a randomized European study. N Engl J Med 2009; 360: 1320-8
3. Loeb S, Bjurlin M, Nicholson J, et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol 2014; 65: 1046-55.
4. Roobol MJ, Schroeder F. The rate of overdiagnosis inextricably linked to prostate-specific antigen-based screening for prostate cancer can be quantified in several ways, but what is the practicable message? Eur Urol 2014; 64: 1056-57.
5. Arnsrud Godtman R, Holmberg E, Lilja H et al. Opportunistic testing versus randomized prostate specific antigen screening: outcome after 18 years in the Goteborg randomized population-based prostate cancer screening trial. Eur Urol 2015; 68: 354
6. Schroder FH, Hugosson J,Roobol MJ, et al. Screening and prostate cancer motality: results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027
7. Hayes JH, Barry MJ. Screening of prostate cancer with the prostate specific antigen test: a review of current evidence. JAMA 2014; 311: 1143.
8. Sattin P, Carlsson S, Holmstrom B, et al. Prostate cancer mortality in areas with high and low prostate cancer incidence. N Natl Cancer Inst 2013; 105: 719-25
9. Zhang L, Zhao F, Liang Z, et al. Effect of anti-human IgM antibody on the proliferation, apoptosis anch cell cycle of Hep-2 laryngeal squamous cell carcinoma cells and potential mechanism underlying its antitumor activity. Int J Clin Exp Pathol 2017; 10: 858-868
10. Mossad NA, Mahmoud EH, Osman EA, et al. Evaluation of squamous cell carcinoma antigen -immunoglobulin M complex (SCCA-IgM) and alpha-L-flucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma. Tumor biol 2014; 35: 11559-64
11. 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
12. Bandiera E, Zanotti L, Fabricio AS, et al. Cancer antigen 125, human epididymis 4, kallicrein 6, osteopontin and soluble mesothelin related peptide immunocomplexed with immunoglobulin M in epithelial ovarian cancer diagnosis. Clin chem Lab Med 2013; 51: 1815-24
13. Wang H, Cao X, Liu EC, et al. Prognostic significance of immunoglobulin M overexpression in laryngeal squamous cell carcinoma. Acta Otolaryngol 2013; 133: 1080-7
14. Gallotta A, Giannarini G, Laurini L, et al. Clinical validation of the iXip index in avoiding unnecessary prostate biopsy: results from a prospective multicenter study involving 426 patients. Cancer Treat Res Comm 2017; 10: 40-45.
15. Sutcliffe P, Hummel S, Simpson E, et al. Use of classical and nover biomarkers as prognostic risk factors for localized prostate cancer: a systematic review.Health Technol Assess 2009; 13: 1-2019.
16. Freedland SJ. Screening, risk assessment, and the approach to therapy in patients with prostate cancer. Cancer 201; 117: 1123-35
17. Kusuda Y, Miyake H, Kurahashi T, et al. Assessement of optimal target genes for detecting micrometastases in pelvic lymph nodes in patients with prostate cancer undergoing radila prostatectomy by real-time reverse transcriptase-polymerase chain reaction. Urol Oncol 2011; 31: 615-21.
18. Tosoian JJ, Loeb S, Ketterman A, 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: 422-29.
19. Turkbey B, Brown AM, Sankieni S, et al. Multiparametric prostate magnetic resonance imaging in the evaluation of prostate cancer. CA Cancer J Clin 2016; 66: 326-36.
20. Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of paired validating confirmatory study. Lancet 2017; 389:815-22
21. 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
22. Van der Leest M, Cornel E, Israel B, et al. Head-to-head comparison of transrectal ultrasoud-guided prostate biopsy versus multiparametric prostate resonance imaging with subsequent magnetic resonance-guided biopsy in biopsy-naive men with elevated Prostate-Specific Antigen: a large prospective multi center clinical study. Eur Urol 2019; 75: 570-8.
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.
24. Boegemann M, Stephan C, Cammann H, et al. The percentage of prostatespecific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years. BJU Int 2016;117:72–9.
25. Na R, Ye D, Liu F, et al. Performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population. Prostate 2014;74:1569–75.
26. 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







How to Cite

Ziglioli F, Granelli G, Cavalieri D, Bocchialini T, Maestroni U. What chance do we have to decrease prostate cancer overdiagnosis and overtreatment? A narrative review. Acta Biomed [Internet]. 2019 Dec. 23 [cited 2024 Jul. 19];90(4):423-6. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/9070