The Association of PSA-IGM and Total PSA Improves the Diagnosis of Prostate Cancer (2009)

Background and aim The specific causes of prostate cancer (Pca) are unknown but the main risk factors of tumor development are associated with age, genetic factors, ethnicity, diet and lifestyle. Prostate cancer is rare in men under 45 years of age, but becomes more common with advancing age. The main diagnostic tools for demonstrating the presence of PCa include digital rectal examination, transrectal ultrasonography, and serum measurement of prostate specific antigen (PSA) followed by prostate biopsy for confirmation of the diagnosis. While the measurement of PSA levels has revolutionized the diagnosis of PCa, it has also increased its overdiagnosis due to the poor diagnostic accuracy. Scientific evidence indicates that biomarkers for different types of cancer such as liver and colorectal cancer circulate in the blood associated with immunoglobulin M (IgM) to form complexes that allow a better diagnosis in comparison to circulating free biomarkers. In prostate cancer it has been demonstrated that testing for serum levels of the PSA-IgM immune complex improves the diagnostic performance of total PSA. The aim of this study was to evaluate the diagnostic accuracy of PSA-IgM compared to total PSA for the selection of patients to be submitted to transrectal ultrasound-guided prostate biopsy. Patients and methods Serum samples from 67 male patients, 33 affected by PCa with a Gleason score from 5 to 7, and 34 affected by benign prostate hypertrophy (BPH), were collected by the Department of Urology of the Spedali Civili of Brescia. The samples were immediately snap frozen at −80°C. Serum levels of PSA-IgM were assessed using Prostate-IC (Xeptagen, Italy) while PSA levels were determined with the Immulite 2000 of Medical Systems S.p.A. Results Patients were stratified into 2 groups according to age; the first group consisted of 24 patients with PCa and 20 with BPH aged between 60 and 70 years and the second group consisted of 9 patients with PCa and 14 with BPH aged between 70 and 80 years. Serum levels of PSA and PSA-IgM were analyzed in the 2 groups using cutoff values of 4 ng/mL for PSA and 145 AU/mL for PSA-IgM. In the first group, 1 8 of 24 PCa patients were positive for PSA (75% sensitivity) with a specificity of 50% (10 of 20 BPH patients), and 1 0 of 24 PCa patients were positive with the PSA-IgM assay (42% sensitivity), which had a higher specificity (70%; 6 of 20 BPH patients). The combination of both biomarkers resulted in a sensitivity of 38% (9 of 24 patients with PCa) but showed a significant improvement in specificity up to 90%, since 18 of 20 patients with BPH were negative for at least one test. In the second group of patients aged 70 to 80 years, the PSA test had a sensitivity of 67% (6/9 PCa patients) and a specificity of 78% (3/14 BPH patients) compared with a sensitivity of 44% for the PSA-IgM test (4/9 PCa patients) with a specificity of 71% (4/14 BPH patients). The combination of PSA and PSA-IgM had a sensitivity of 30% (3/9) but the highest specificity (93%, 13/14 BPH patients). Conclusion The results of the study demonstrate the diagnostic value of the PSA-IgM assay compared with the total PSA test. The combination of PSA-IgM with total PSA was the best approach to reduce the number of false-positive results, thus improving the diagnosis of prostate cancer.