The Role of Prostate-Specific Antigen Density in Men with Low-Risk Prostate Cancer Suitable for Active Surveillance: Results of a Prospective Observational Study

PSA density has been considered a valuable tool to decide whether to treat in active surveillance (AS) setting for low risk prostate cancer (PCa) in many ongoing AS protocols, such as PRIAS.¹ At present time, a PSA density of <0.15ng/ml/cc is considered a threshold for AS in the current European Association of Urology Guidelines.² However, the correct threshold is still debated and not yet clearly assessed, especially due to the inter-operator variability of prostate volume determination through ultrasounds, which may affect its value and thus our possibility to outline a correct threshold.³

With our study, we prospectively evaluated a series of patients that were submitted to random prostate biopsy for suspect of PCa. Data of subsequent definitive pathology for whom underwent a radical prostatectomy in PCa positive biopsies were also collected. Differently for studies reported in the literature, prostate volume was established at biopsy time from two expert urologists, thus minimizing the inter-operator variability error in its calculation. We focused especially on patients who would have been a candidate to AS that decided to undergo radical prostatectomy. Upgrading and upstaging data were collected and we established through statistical analysis a cut-off for PSA density to determine an upstaging in risk class for low-risk PCa.⁴

In our results, we found that PSA density was clearly associated with both upgrading and upstaging in low-risk PCa with an odds ratio (OR) 10.01, 95% confidence interval (CI) 5.06-15.60, and p=0.024. Furthermore, through ROC curve we determined in our data a cut-off of 0.185 of PSA density to find upstaging in radical prostatectomy for low-risk PCa with an area of 0.899±0.068 (95% CI: 0.766-1.000). Despite the small number of patients enrolled, 746 of whom just 52 with low-risk PCa who underwent radical prostatectomy, it is important to underline that 36 of them (69.2%) had upstaging at definitive pathology. Only a small proportion of these patients could have been submitted to AS with no further risks, and this was the actual scenario in PCa treatment until 2018.

Currently, multiparametric Magnetic Resonance Imaging (mpMRI) has been implemented in clinical practice before biopsy after the PRECISION trial, thus allowing us to avoid unnecessary biopsies and overtreatment of clinically insignificant PCa.⁵ This imaging methodic may also increase our capability to correctly calculate PSA density. Therefore, a more precise implementation of PSA density with PI-RADS score should be advocated, especially in score 3 patients, thus reducing unnecessary treatments and diagnostic assessments. Our results may be implemented in this scenario because we found and defined a correlation for clinically significant PCa and PSA density, confirmed at radical prostatectomy in a prospective setting.
Further studies with larger samples would be necessary to found a correct cut-off to decide whether to treat in AS setting with PSA density in low-risk PCa, hopefully with an available mpMRI to be fully implemented in daily clinical practice.

Written by: Simone Morselli, Arcangelo Sebastianelli, Mauro Gacci, and Sergio Serni, Department of Minimally Invasive and Robotic Urological Surgery and Kidney Transplantation, Careggi Hospital, University of Florence, Florence, Italy

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