Prognostic Impact of Increased Prostate-Specific Antigen Density in Men on Active Surveillance for Prostate Cancer
Dimitar Zlatev, MD; Keyan Salari, MD, PhD; David Kuppermann, MD; Daniel Pucheril, MD, MBA; Michael L. Blute, MD; Adam Feldman, MD
Massachusetts General Hospital, Boston, MA
BACKGROUND: Active surveillance (AS) is an increasingly utilized option in the management of appropriately selected men with prostate cancer. Prostate-specific antigen (PSA) density at diagnosis is an important predictor of disease progression, however subsequent change in PSA density has not been thoroughly assessed. We sought to investigate the prognostic impact of post-diagnostic PSA density in men on AS.
METHODS: Within our institutional database of men enrolled in AS for low-risk and favorable intermediate-risk prostate cancer between 1997-2014, we retrospectively identified 335 patients with PSA density measurements both at diagnosis and during AS. PSA density was calculated as PSA divided by prostate volume estimated by transrectal ultrasonography. The primary outcome was treatment-free survival. Secondary outcomes were adverse pathology on radical prostatectomy, metastasis-free survival (MFS), disease-specific survival (DSS), and overall survival (OS). Survival analyses were conducted using the Kaplan-Meier method and Cox proportional hazards regression.
RESULTS: At diagnosis, median age was 66 years (IQR 60-71) and median PSA was 5.0 ng/mL (IQR 3.8-6.8). The vast majority of patients had Gleason ≤ 6 (98%) and clinical stage T1 (93%) disease. During AS, median follow-up was 4.3 years (IQR 2.7-5.6), median PSA measurements were 11 (IQR 7-16), and median prostate volume measurements were 2 (IQR 2-3). Among the 335 patients in the cohort, 100 (30%) progressed to treatment for the following reasons: pathologic progression (77%), PSA progression (16%), patient preference (5%), and other reasons (2%). Among the 100 treated patients, 30 (30%) underwent radical prostatectomy and 6 (6%) had pT3 disease on surgical pathology. On univariate analysis, predictors of progression to treatment included PSA density ≥ 0.15 ng/ml/ml at diagnosis (p = 0.02), involvement of greater than 20% of any core on diagnostic biopsy (p = 0.02), involvement of 2 or more cores on diagnostic biopsy (p = 0.01), and an increase in PSA density on AS (p = 0.02). On multivariate analysis, increase in PSA density on AS remained a significant predictor of progression to treatment (HR 1.57, 95% CI 1.02-2.39, p = 0.04). Increase in PSA density on AS was not associated with MFS, DSS, or OS.
CONCLUSIONS: Increase in PSA density in men on AS for prostate cancer is associated with a higher rate of progression to treatment. With the increased utilization of imaging in the management of these patients, increase in PSA density may represent an important adjunct measure for prognostication of men on AS.
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