Prognostic Significance of The Nadir Prostate Specific Antigen Level After Hormone Therapy for Prostate Cancer

Abstract

We determine whether the nadir prostate specific antigen (PSA) level after hormone therapy can be used to predict the progression to hormone refractory prostate cancer. We reviewed the progressive status and survival of 177 patients with stage C or D prostate cancer who had received hormone therapy at our institution. The overall survival rate, incidence of progression to hormone refractory prostate cancer and interval until progression were analyzed with reference to the nadir PSA level. Multiple regression analysis was used to analyze the predictive factors for progression to hormone refractory prostate cancer, and the relative efficacy of the nadir PSA level in predicting progression was evaluated by receiver operating characteristics analysis. Median followup was 39 months (range 3 to 89) and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had progression to hormone refractory prostate cancer. Median time until nadir PSA levels were reached after hormone therapy was 8.1 months and median time until hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10 ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar clinicopathological characteristics. Nadir PSA levels correlated significantly with pretreatment PSA levels, Gleason scores and progression to hormone refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and inversely correlated with the interval to the establishment of hormone refractory prostate cancer (r = −0.465, p <0.05). By univariate analysis bone metastasis, nadir PSA, PSA at 6 months after treatment and pretreatment PSA were significantly associated with progression to hormone refractory prostate cancer. Only the nadir PSA was calculated to be an independent factor by multivariate analysis. Receiver operating characteristics analysis indicated that nadir PSA predicted progression to hormone refractory prostate cancer after 2 years with an accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1 ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an independent prognosticator for survival, as were initial levels of hemoglobin and alkaline phosphatase. The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.