Distinct prognostic role of prostate-specific antigen doubling time and velocity at emergence of androgen independence in patients treated with chemotherapy.

Objective: To investigate whether the prostate-specific antigen doubling time (PSADT) and velocity (PSAV) at the emergence of androgen-independent prostate cancer (AIPC) provide independent prognostic information.

Methods: Patients treated with chemotherapy were identified in an institutional prostate cancer database. The PSADT was calculated using PSA values from the first increase greater than the PSA nadir during androgen deprivation therapy until the start of the next treatment. The PSAV was calculated using the same PSA values over time. The association with overall survival (OS) from the date of AIPC was analyzed using the Cox proportional hazards regression model.

Results: PSADT and PSAV at the emergence of AIPC were calculated in 91 patients. On univariate analysis, a shorter PSADT and greater PSAV were associated with decreased OS. On multivariate analysis, a PSADT of 12 weeks or less (hazard ratio 3.2), PSAV greater than 10 ng/mL/yr (hazard ratio 2.8), PSA nadir greater than 0.2 with ADT, low hemoglobin, and type of chemotherapy persisted as significant predictors of decreased OS (each P <0.01). A rapid PSADT (12 weeks or less) and high PSAV (greater than 10 ng/mL/yr) predicted for the worst prognosis (25 months median OS, unadjusted). A slow PSADT (greater than 12 weeks), and low PSAV (10 ng/mL/yr or less) predicted for the best prognosis (75 months); other combinations had intermediate prognoses (49 and 50 months).

Conclusions: The PSAV at the start of AIPC contributes prognostic information independent of the PSADT in patients receiving chemotherapy. Future studies should investigate the relative contribution of each of these factors in predicting survival.