2032 POSSIBLE PITFALLS IN USING PROSTATE SPECIFIC ANTIGEN VELOCITY FOR DETECTION OF PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVES: Prostate Specific Antigen (PSA) is a well-documented marker for prostate cancer (CaP). PSA velocity (PSAV) is a derivative that has been used to increase PSA performance characteristics for CaP detection. Elevated PSAV may be an early sign of underlying CaP, but has somewhat limited sensitivity and specificity. Explanations for false-positive PSAV include missed CaP on biopsy; prostatitis; or assay standardization bias. Reasons for false-negative PSAV include very low volume CaP or high grade CaP (severely de-differentiated cells produce less PSA); prior, resolved prostatitis; or assay standardization bias. METHODS: We assessed patients who underwent prostate biopsy after prior screening with 3 PSA blood tests. PSAV was calculated using linear regression. Elevated PSAV was defined as change in PSA 0.35 ng/mL/yr. After stratifying based on PSAV, we specifically examined: 1) patients with an elevated PSAV but no CaP on biopsy and 2) patients with low PSAV but CaP on biopsy. RESULTS: Between 2003 and 2010, 1358 patients underwent prostate biopsy after previous screening with 3 PSA tests. 106 had PSAV 0.35 ng/mL/yr and negative biopsy. Of these, 62 (58%) had CaP on biopsy at a later date, suggesting negative biopsy at the time of elevated PSAV may have been due to missed early, low volume CaP. 10 (9.4%) biopsies revealed prostatic intraepithelial neoplasia (PIN), also suggesting a possibly missed small CaP. 12 biopsies (11.3%) had signs of prostatitis. In the remaining 22 (20.7%), cause for elevated PSAV was not readily apparent; transient inflammation, prostatic trauma, or assay standardization bias may have played a role. 480 patients with PSAV 0.35 had CaP on biopsy. Of these, 22 (4.6%) had a Gleason 8–10 tumor. 464 were treated with radical prostatectomy. Surgical pathology for 266 (55.4%) revealed total CaP volume 5% of submitted tissue. Of the remaining patients, 30% had possibly slow growing Gleason 6 tumors involving 6–20% of submitted tissue, and 54% had Gleason 7 tumors. In some cases, assay standardization bias or prior resolved prostatitis may have caused the spuriously low PSAV. CONCLUSIONS: Nearly 80% of patients with false-positive PSAV had an easily explained confounder-missed CaP or prostatitis. Nearly 60% of patients with false-positive PSAV were eventually found to have CaP, underscoring the need to closely follow a patient’s PSA despite initial negative biopsy. False-negative tests can often be explained by low volume or high Gleason grade disease, prior resolved prostatitis, or possible PSA assay standardization bias.