A Comparative Performance Analysis of Total PSA, Percentage Free PSA, PSA Velocity, and PSA Density versus the Detection of Primary Circulating Prostate Cells in Predicting Initial Prostate Biopsy Findings in Chilean Men

Abstract

Introduction. PSA parameters have been used in an attempt to improve the diagnostic yield of prostate screening tests; the detection of primary malignant circulating prostate cells (CPCs) may improve the diagnostic yield of screening and therefore avoid unnecessary biopsies. Patients and Methods. Prospective study of all men undergoing initial prostate biopsy due to an elevated total serum PSA. Free percent PSA, PSA velocity, and PSA density were determined. Primary CPCs were detected using standard immunocytochemistry. A positive test for CPCs was defined as one cell PSA (+) P504S (+) in an 8 ml blood sample. Positive predictive and negative predictive values, specificity, and sensitivity were calculated for each test as well as the number of biopsies avoided and cancers missed. Results. 303 men participated in the study of whom 113/303 (37.3%) men had prostate cancer. Of the three PSA based parameters, free percent PSA was superior, sensitivity 70.8%, and specificity 67.4%. Primary CPCs detection had a sensitivity of 88.5% and a specificity of 88.4% avoiding 181 (59.7%) biopsies, detecting 93/95 (98%) of clinically significant cancers, and missing 13 (11.5%) low grade, small volume tumors. Conclusions. The use of primary CPCs as a sequential test could decrease the number of initial prostate biopsies missing those cancers which are treated by active observation.

The Ethical Dilemma Surrounding Prostate Specific Antigen (PSA) Screening

“…In the absence of cost-effective screening techniques, scientists and researchers alike have been exploring modifications of the PSA for aiding in diagnosis. Several modifications have been suggested such as the free versus total PSA, PSA density of the transition zone, agespecific PSA, PSA velocity and PSA doubling time, serial PSA and Pro-PSA [41][42][43]. Among these PSA velocity, or the study of PSA dynamics over time, has generated yet another controversy.…”

Extended use of P504S Positive Primary Circulating Prostate Cell Detection to Determine the Need for Initial Prostate Biopsy in a Prostate Cancer Screening Program in Chile

“…Thus men CPC negative but with an increased serum PSA could be observed rather than evaluated with a prostate biopsy, with all its inherent risks. In comparison with free PSA, PSA velocity and PSA density, the use of primary CPC detection was shown to be superior (Murray et al, 2014) Studies detecting circulating prostate cells, using different methodologies have been discordant results. Using a dual PSA/prostate specific membrane antigen RT-PCR method Eschwege et al (2009) only found 37% of pre-operative patients to be CPC positive.…”

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level

“…The traditional cut-off for an abnormal PSA level in the major screening studies has been 4.0 ng/mL though the sensitivity has been reported as being between 67% and 80% with a low specificity of only 20%–30% [13] , [14] . When the PSA level of 4 ng/mL was used in our validation dataset, the sensitivity was 96%, however with a severely low specificity of 10.4%.…”