Prostate-Specific Antigen Kinetics During Follow-Up Are an Unreliable Trigger for Intervention in a Prostate Cancer Surveillance Program

Abstract

Purpose To assess the predictive ability of prostate-specific antigen (PSA) velocity (PSAV) and doubling time (PSADT) for biopsy progression and adverse pathology at prostatectomy among men with low-risk prostate cancer enrolled on an active-surveillance program. Methods We evaluated 290 men who met criteria for active surveillance (ie, PSA density < 0.15 ng/mL/cm3 and Gleason score ≤ 6 with no pattern ≥ 4, involving ≤ 2 cores with cancer, and ≤ 50% involvement of any core by cancer) with two or more serial PSA measurements after diagnosis from 1994 to 2008. Follow-up included twice-yearly digital rectal exam and PSA measurements and yearly surveillance biopsy. Treatment was recommended for biopsy progression (ie, Gleason score ≥ 7, or > 2 positive cores, or > 50% core involvement). Sensitivity and specificity of postdiagnostic PSAV and PSADT were explored by using receiver operating characteristic (ROC) analysis. Results Overall, 188 (65%) men remained on active surveillance, and 102 (35%) developed biopsy progression at a median follow-up of 2.9 years. PSADT was not significantly associated with subsequent adverse biopsy findings (P = .83), and PSAV was marginally significant (P = .06). No PSAV or PSADT cut point had both high sensitivity and specificity (area under the curve, 0.61 and 0.59, respectively) for biopsy progression. In those who eventually underwent radical prostatectomy, PSAV (P = .79) and PSADT (P = .87) were not associated with the presence of unfavorable surgical pathology. Conclusion Postdiagnostic PSA kinetics do not reliably predict adverse pathology and should not be used to replace annual surveillance biopsy for monitoring men on active surveillance.