BERKELEY, CA (UroToday.com) - ProPSA represents a distinct form of fPSA that demonstrates greater disease-association than PSA, fPSA or f/tPSA alone.
Truncated forms of proPSA were found to be elevated in peripheral zone cancer tissue compared with BPH tissues. The [-2]proPSA has received the most attention since it was the primary form found in tumor extracts and shows higher immunostaining in prostate tumor than benign tissue, and in vitro is the most stable of the five identified proPSA forms.
Guazzoni et al. showed that in patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy. These findings are particularly worthy as they have been achieved under a high standard protocol study: the population was representative of contemporary men seeking urological consultation (contemporary cohort of candidates for a prostate biopsy), the biopsy scheme applied a specific extended (18-22 core) bioptic protocol, resulting in a high detection rate, all the samples were analysed by an experienced uro-pathologist, the enrolment was prospective, blood samples were analyzed according to p2PSA product insert claimed stability information and no -70°C stored serum was included. A sub analysis of data allowed drawing further information.
Characterization of p2PSA in patients with high-grade prostatic intraepithelial neoplasia (HGPIN): In our population, bioptic pathological detected HGPIN was found in 21 (8.5%) of subjects. P2PSA (p<0.05), %p2PSA (p<0.001) and phi (p<0.001) values were significantly higher in the cancer group towards HGPIN group, but not tPSA, fPSA and %fPSA; no differences were found between BPH group and HGPIN group in median values of all these predictive variables, whereas 2proPSA (p<0.005) %p2PSA (p<0.001) and phi (p<0.001) values were significantly higher and %fPSA (p<0.005) values significantly lower in the cancer group towards the BPH group.
In their clinical practice, most urologists need a cut-off as they do for tPSA and f/tPSA. A sub-analysis showed that at a cut-off of 1.66, sensitivity and specificity of %p2PSA were 71.3% (95%C.I 61.8-79.6), and 70.7% (95%C.I 63.5-77.2) respectively. At a cut-off of 38, sensitivity and specificity of phi were 68.2% (95%C.I 58.5-76.9), and 67.6% (95%C.I 60.2-74.4) respectively. In a real life simulation using such cut-offs, %p2PSA and phi would have been avoided unnecessary biopsies while missing a low percentage of significant PCa in a set of contemporary men undergoing prostate biopsy.
There are several factors that are associated with the abnormal elevation of sPSA concentration such as aging, BPH, prostate volume, diagnostic and therapeutic procedure, and cancer. With respect to the inflammation, acute bacterial prostatitis is well known for elevating the sPSA remarkably, but a controversy exists about whether the non-bacterial asymptomatic histologic inflammation correlated with sPSA concentration. Recently, several authors confirmed that the histologic inflammatory infiltration with glandular epithelium disrupted might be a significant contributor to elevated sPSA levels in patients with exclusive BPH and they concluded that in assessment of negative needle biopsy specimens of the prostate, a description of histologic inflammatory infiltrates in specimens, especially prostatic epithelium integrity, will be helpful in interpreting the abnormal elevation of sPSA levels and avoiding unnecessary repeated biopsies. Our study showed that p2PSA and its derivates, %p2PSA and phi, could discriminate between patients with or without PCa in a range of tPSA between 2.0 and 10 ng/mL. So far no study correlated the serum level of [-2]proPSA and prostatic inflammation. One of the further studies will be to investigate the correlation between the serum [-2]proPSA, %p2PSA and phi and pathological proved prostatic inflammation in men undergoing prostate biopsy for suspected PCa.
Massimo Lazzeri, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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 - Abstract